CEREBRAL AND CEREBELLAR CORTICES AND NUCLEI: MODULE 8

Reading requirements:

Principles of Neural Science, Third Edition, Kandel, Schwartz and Jessel: Pages 627-645

 

Bibliography

 

The following references have been utilized by Prof Carrick in the

preparation of his lecture on the cerebellum. Learners should

review the annotated bibliographies and refer to texts of their

choice for review of anatomy and physiology of the cerebellum.

Prof Carrick's lecture is specific to clinical applications

involving a variety of cerebellar based syndromes using

nonpharmaceutical and non surgical interventions.

1. Abe, K.; Ukita, H.; Yorifuji, S.; Yanagihara, T. Crossed cerebellar

diaschisis in chronic Broca's aphasia. Neuroradiology. 1997

Sep; 39(9): 624-6; ISSN: 0028-3940.

GERMANY. The cerebellum has anatomical connections to the

cerebral cortex, through which it can affect language function.

To study these connections, we investigated patients with

chronic Broca's aphasia using MRI and single-photon emission

computed tomography (SPECT). We selected 15 such patients (9

male, 6 female, aged 17-64 years, mean age 56 years) from 30

chronically aphasic patients. Using the results of SPECT, we

divided them into patients with (group 1) and without (group

2) crossed cerebellar diaschisis (CCD). We compared the

language function of the two groups. Patients in group 1

showed classical Broca's aphasia, while patients in group 2

showed mainly word-finding difficulty. Patients with CCD hat

infarcts involving the lower part of the frontal gyrus but

patients without CCD did not, which suggests that this region

may have functional and anatomical connections with the

cerebellum. Our findings support the notion that the

cerebellum contributes to language.

2. Adams, S. R.; Lev, Ram V.; Tsien, R. Y. A new caged Ca2+, azid-1, is

far more photosensitive than nitrobenzyl-based chelators.

Chem-Biol. 1997 Nov; 4(11): 867-78; ISSN: 1074-5521.

ENGLAND. BACKGROUND: Photolabile chelators that release

Ca2+ upon illumination have been used extensively to dissect

the role of this important second messenger in cellular

processes such as muscle contraction and synaptic

transmission. The caged calcium chelators that are presently

available are often limited by their inadequate changes in Ca2+

affinity, selectivity for Ca2+ over Mg2+ and sensitivity to

light. As these chelators are all based on nitrobenzyl

photochemistry, we explored the use of other photosensitive

moieties to generate a new caged calcium with improved

properties. RESULTS: Azid-1 is a novel caged calcium in which

a fluorescent Ca2+ indicator, fura-2, has been modified with

an azide substituent on the benzofuran 3-position. Azid-1

binds Ca2+ with a dissociation constant (Kd) of approximately

230 nM, which changes to 120 microM after photolysis with

ultraviolet light (330-380 nm). Mg2+ binding is weak (8-9 mM

Kd) before or after photolysis. Azid-1 photolyzes with unit

quantum efficiency, making it 40-170-fold more sensitive to

light than caged calciums used previously. The photolysis of

azid-1 probably releases N2 to form a nitrenium ion that adds

water to yield an amidoxime cation; the electron-withdrawing

ability of the amidoxime cation reduces the chelator's Ca2+

affinity within at most 2 ms following a light flash. The

ability of azid-1 to function as a caged calcium in living cells

was demonstrated in cerebellar Purkinje cells, in which Ca2+

photolytically released from azid-1 could replace the normal

depolarization-induced Ca2+ transient in triggering synaptic

plasticity. CONCLUSIONS: Azid-1 promises to be a useful tool

for generating highly controlled spatial and temporal

increases of Ca2+ in studies of the many Ca2+-dependent

biological processes. Unlike other caged calciums, azid-1 has a

substantial cross section or shows a high susceptibility for

two-photon photolysis, the only technique that confines the

photochemistry to a focal spot that is localized in three

dimensions. Azide photolysis could be a useful and more

photosensitive alternative to nitrobenzyl photochemistry.. 0;

0; 67-42-5; 7440-70-2; 85233-19-8.

3. Alavi, A.; Mirot, A.; Newberg, A.; Alves, W.; Gosfield, T.; Berlin, J.;

Reivich, M.; Gennarelli, T. Fluorine-18-FDG evaluation of

crossed cerebellar diaschisis in head injury. J-Nucl-Med. 1997

Nov; 38(11): 1717-20; ISSN: 0161-5505.

UNITED-STATES. This study investigates the phenomenon of

crossed cerebellar diaschisis in head injury patients.

METHODS: We visually compared fluorine-18-

fluorodeoxyglucose (FDG)-PET images to radiograph computed

tomography or magnetic resonance images in 19 patients with

head injury. RESULTS: We found that of 68 focal unilateral

lesions, 40% were associated with contralateral cerebellar

hypometabolism and 19% were associated with ipsilateral

cerebellar hypometabolism. Of supratentorial,

extraparenchymal lesions (n = 20), 45% were associated with

contralateral cerebellar hypometabolism, whereas 15% had

ipsilateral cerebellar hypometabolism. Intraparenchymal

lesions were associated with contralateral cerebellar

hypometabolism in 38% of the patients and with ipsilateral

cerebellar hypometabolism in 21% of the patients. Of the

cortical lesions that were the patients' most severe injury,

69% were associated with contralateral cerebellar

hypometabolism, whereas only 8% were associated with

ipsilateral cerebellar hypometabolism. In patients with focal

supratentorial lesions alone, 50% of all focal lesions were

associated with contralateral cerebellar hypometabolism and

13% had ipsilateral hypometabolism. Of patients with both

focal and diffuse brain injuries, 27% of the focal lesions had

contralateral cerebellar hypometabolism and 27% had

ipsilateral cerebellar hypometabolism to the most severe

focal injury. CONCLUSION: Crossed cerebellar diaschisis is

seen more often in patients with focal cortical or

extraparenchymal injuries and is not seen in patients with

multiple or diffuse brain injuries. Furthermore, this

predominance is more pronounced with lesions of the greatest

severity.. 0; 63503-12-8.

4. Anderson, C. W.; Keifer, J. The cerebellum and red nucleus are not

required for In vitro classical conditioning of the turtle

abducens nerve response. J-Neurosci. 1997 Dec 15; 17(24):

9736-45; ISSN: 0270-6474.

UNITED-STATES. The role of the cerebellum during motor

learning is a controversial issue. Many authors have suggested

that the cerebellum and its connections with the red nucleus

are essential for the acquisition of the conditioned eye blink

reflex. Although there is little argument that the cerebellum

is an important component to the generation of the conditioned

response (CR), a number of studies have suggested that the

cerebellum is not essential for conditioning. Using an in vitro

model of the classically conditioned turtle abducens nerve

response, we investigated the effect of cerebellar and red

nucleus lesions on the acquisition, extinction, and

reacquisition of CRs. Neural discharge was recorded from the

abducens nerve after a single shock unconditioned stimulus

(US) was applied to the ipsilateral trigeminal nerve. When the

US was paired with a conditioned stimulus (CS) applied to the

posterior eighth, or auditory, nerve, a positive slope of CR

acquisition was recorded in the abducens nerve. After

extinction stimuli in which the CS and US were alternated, the

number of CRs decreased to near zero. When the CS and US

were once again paired, reacquisition at a faster rate was

recorded. The CRs showed unusual timing features compared

with preparations in which the cerebellum was intact; they

had significantly shorter latencies and showed burst-like

responses. These data demonstrate that it is possible to

classically condition this in vitro preparation in the absence

of the cerebellum and red nucleus. However, the latencies of

CRs were found to be dramatically altered in the cerebellar-

lesioned preparations, suggesting that the cerebellum does

play a role in the timing of the CR.

5. Anderson, C. W.; Nishikawa, K. C. The functional anatomy and

evolution of hypoglossal afferents in the leopard frog, Rana

pipiens. Brain-Res. 1997 Oct 17; 771(2): 285-91; ISSN: 0006-

8993.

NETHERLANDS. Previously, we suggested that afferents are

present in the hypoglossal nerve of the leopard frog, Rana

pipiens. The basis for this was behavioral data obtained after

transection of the hypoglossal nerve. These afferents

coordinate the timing of tongue protraction with mouth

opening during feeding. The goal of the present study was to

define anatomically these hypoglossal afferents in Rana

pipiens. Retrograde tracing was performed using horseradish

peroxidase, fluorescent dextran amines and neurobiotin. Data

show that the cell bodies of hypoglossal afferents are located

in the dorsal root ganglion of the third spinal nerve and enter

the brainstem through its dorsal root. The afferents ascend in

the dorsomedial funiculus and move laterally after they pass

the obex. They project in the granular layer of the cerebellum

and the medial reticular formation. The cervical afferents that

travel in this pathway are known to carry proprioceptive and

cutaneous sensory information. We hypothesize that the

presence of afferents in the hypoglossal nerve is a derived

characteristic of anurans, which has resulted from the re-

routing of afferent fibers from the third spinal nerve into the

hypoglossal nerve. The appearance of hypoglossal afferents

coincides with the morphological acquisition of a highly

protrusible tongue.. EC 1.11.1.-.

6. Antkowiak, B.; Hentschke, H.; Kirschfeld, K. Effects of volatile

anaesthetics on spontaneous action potential firing of

cerebellar Purkinje cells in vitro do not follow the Meyer-

Overton rule. Br-J-Anaesth. 1997 Nov; 79(5): 617-24; ISSN:

0007-0912.

ENGLAND. We have investigated in rat brain slices the effects

of the volatile anaesthetics enflurane, isoflurane and

halothane on spontaneous discharge patterns and mean firing

rates of cerebellar Purkinje cells. In the absence of these

anaesthetics, Purkinje cells fired bursts of action potentials

separated by quiescent periods lasting less than 2 s. Mean

discharge rates were 10.8 (SEM 0.4) Hz at 23 +/- 1 degrees C

and 25.6 (1.2) Hz at 35 +/- 1 degrees C. The agents exhibited

qualitatively different effects when applied at concentrations

corresponding to 1-3 MAC. Enflurane markedly lengthened

burst and inter-burst durations. Isoflurane acted in a similar

manner, but effects were less pronounced. In contrast with

isoflurane and enflurane, halothane shortened burst durations.

At concentrations corresponding to 1-1.5 MAC, halothane,

isoflurane and enflurane significantly depressed action

potential firing by 15-30% (P < 0.05). Enflurane 1.2 mmol

litre-1 (2.0 MAC), isoflurane 0.9 mmol litre-1 (2.8 MAC) and

halothane 0.9 mmol litre-1 (3.8 MAC) depressed spontaneous

spike rates by 50%. The changes in discharge patterns and the

concentration-dependent decrease in the firing rates were

similar at 23 +/- 1 degrees C and 35 +/- 1 degrees C. In

summary, we observed that neither the anaesthetic-induced

alterations in spontaneous discharge patterns nor the EC50

values of the concentration-dependent depression of the mean

firing rates were in accordance with the Meyer-Overton rule.

However, at clinically relevant concentrations, depression of

average spike rates did not differ significantly between the

anaesthetics and thus followed the rule. Our results suggest

that anaesthetic actions, which are in accordance with the

rule, are frequently masked by several side effects.. 0;

13838-16-9; 151-67-7; 26675-46-7.

7. Arai, A.; Sato, M.; Hozumi, I.; Matsubara, N.; Tanaka, K.; Soma, Y.;

Adachi, T.; Tsuji, S. Cerebellar ataxia and peripheral

neuropathy due to chronic bromvalerylurea poisoning. Intern-

Med. 1997 Oct; 36(10): 742-6; ISSN: 0918-2918.

JAPAN. A patient with chronic bromvalerylurea poisoning

showed cerebellar ataxia and peripheral neuropathy. The

patient was a 42-year-old Japanese man who developed

consciousness disturbance, diplopia, slurred speech, ataxia and

gait disturbance after having taken bromvalerylurea for ten

years. Magnetic resonance imaging revealed atrophy of the

cerebellum and pontine tegmentum. An electrophysiological

study revealed decreased motor nerve conduction velocity and

amplitude of compound muscle action potentials of the right

tibial nerve. Histological findings of the left sural nerve

indicated a slightly decreased large myelinated fiber

diameter, which suggested chronic axonal damage.. 0; 496-67-

3.

8. Aruga, J.; Minowa, O.; Yaginuma, H.; Kuno, J.; Nagai, T.; Noda, T.;

Mikoshiba, K. Mouse Zic1 is involved in cerebellar development.

J-Neurosci. 1998 Jan 1; 18(1): 284-93; ISSN: 0270-6474.

UNITED-STATES. Zic genes encode zinc finger proteins, the

expression of which is highly restricted to cerebellar granule

cells and their precursors. These genes are homologs of the

Drosophila pair-rule gene odd-paired. To clarify the role of the

Zic1 gene, we have generated mice deficient in Zic1.

Homozygous mice showed remarkable ataxia during postnatal

development. Nearly all of the mice died within 1 month. Their

cerebella were hypoplastic and missing a lobule in the anterior

lobe. A bromodeoxyuridine labeling study indicated a reduction

both in the proliferating cell fraction in the external germinal

layer (EGL), from 14 d postcoitum, and in forward movement of

the EGL. These findings suggest that Zic1 may determine the

cerebellar folial pattern principally via regulation of cell

proliferation in the EGL.. 0; 0; 0.

9. Atkins, M. J.; Apps, R. Somatotopical organisation within the

climbing fibre projection to the paramedian lobule and copula

pyramidis of the rat cerebellum. J-Comp-Neurol. 1997 Dec 15;

389(2): 249-63; ISSN: 0021-9967.

UNITED-STATES. The climbing fibre projection to the

paramedian lobule (lobule VII) and the copula pyramidis (lobule

VIII) in the posterior lobe of the rat cerebellum was

investigated in pentobarbitone-anaesthetised animals.

Percutaneous electrical stimulation generated climbing fibre

field potentials on the cerebellar surface that indicated a

somatotopical organisation into five distinct cortical areas.

Each area was identified by the site(s) of peripheral

stimulation that evoked the largest response within that area,

and from medial to lateral the cortex was subdivided as

follows [principal site(s) of stimulation in parentheses with

corresponding range of onset latencies]: in the paramedian

lobule, area 1 (contralateral face, 17-18 ms), area 2

(ipsilateral forelimb, 10-15 ms) and area 3 (ipsi- and

contralateral forelimbs, 16-26 ms and 15-30 ms,

respectively); and in the copula pyramidis, area 4 (tail, 17-21

ms) and area 5 (ipsilateral hindlimb, 13-19 ms). In additional

retrograde tracer experiments, small volumes of fluorescent-

tagged beads were injected into each of the different areas

and the location of retrogradely labelled olive cells was

mapped. By comparison with other species, the results

indicate that in the paramedian lobule area 1 corresponds to

zone A2; area 2 corresponds, at least in part, to medial C1; and

area 3 corresponds to C2; in addition, farther laterally, a C3

zone may be present. In the copula pyramidis, areas 4 and 5

correspond to subzones of medial C1. Overall, the results

support the view that a general principle of cerebellar cortical

organisation is a division into parasagittal zones, each

characterised by its somatotopically organised climbing fibre

input that arises from a specific, rostrocaudally oriented

column of cells within the inferior olivary nucleus.

10. Baader, S. L.; Sanlioglu, S.; Berrebi, A. S.; Parker Thornburg, J.;

Oberdick, J. Ectopic overexpression of engrailed-2 in

cerebellar Purkinje cells causes restricted cell loss and

retarded external germinal layer development at lobule

junctions. J-Neurosci. 1998 Mar 1; 18(5): 1763-73; ISSN:

0270-6474.

UNITED-STATES. Members of the En and Wnt gene families

seem to play a key role in the early specification of the brain

territory that gives rise to the cerebellum, the midhindbrain

junction. To analyze the possible continuous role of the En and

Wnt signaling pathway in later cerebellar patterning and

function, we expressed En-2 ectopically in Purkinje cells

during late embryonic and postnatal cerebellar development.

As a result of this expression, the cerebellum is greatly

reduced in size, and Purkinje cell numbers throughout the

cerebellum are reduced by more than one-third relative to

normal animals. Detailed analysis of both adult and developing

cerebella reveals a pattern of selectivity to the loss of

Purkinje cells and other cerebellar neurons. This is observed

as a general loss of prominence of cerebellar fissures that is

highlighted by a total loss of sublobular fissures. In contrast,

mediolateral patterning is generally only subtly affected. That

En-2 overexpression selectively affects Purkinje cells in the

transition zone between lobules is evidenced by direct

observation of selective Purkinje cell loss in certain fissures

and by the observation that growth and migration of the

external germinal layer (EGL) is selectively retarded in the

deep fissures during early postnatal development. Thus, in

addition to demonstrating the critical role of Purkinje cells in

the generation and migration of granule cells, the

heterogeneous distribution of cellular effects induced by

ectopic En expression suggests a relatively late morphogenetic

role for this and other segment polarity proteins, mainly

oriented at lobule junctions.. 0; 0; 0.

11. Balaban, C. D.; Porter, J. D. Neuroanatomic substrates for

vestibulo-autonomic interactions. J-Vestib-Res. 1998 Jan;

8(1): 7-16; ISSN: 0957-4271.

UNITED-STATES. Recent anatomical studies have identified a

network of central neural circuits that appear to integrate

vestibular and autonomic information. Like vestibulo-ocular

and vestibulospinal circuits, these pathways appear to be

under inhibitory modulation by distinct regions in the medial

aspect of the cerebellar cortex. These central circuits have

the potential to explain the known influence of vestibular

stimulation on autonomic motor responses through descending

effects on brain stem autonomic regions. In a more global

context, the extensive convergence of vestibular and

autonomic information in both vestibular and autonomic brain

regions is consistent with the concept that vestibular and

visceral information (for example, blood pooling and visceral

proprioception) are used to form a central representation of

gravitoinertial parameters during movements. This

representation can influence neural circuitry involved in

postural control, cardiovascular control, perception of the

spatial vertical and emotional or affective responses.

12. Baptista, M. V.; Vale, J.; Leitao, O. [Striato-pallido-dentate

calcifications]. Calcificacoes estrio-palido-dentadas. Acta-

Med-Port. 1997 Aug; 10(8-9): 563-7; ISSN: 0870-399X.

PORTUGAL. Striato-pallido-dentate calcifications (SPDC) is a

well defined entity, characterized by calcium deposits in the

basal ganglia, dentate nuclei and the centrum semiovale.

Several metabolic derangements have been associated with

this entity, particularly parathyroid disorders. The traditional

designation of Fahr's syndrome should be restricted to the

idiopathic cases. The authors report a study of seven patients

with SPDC. Hypocalcemia was found in three cases, two with

pseudohypoparathyroidism and one with hypoparathyroidism.

Fahr's syndrome was diagnosed in four patients. Clinical and

laboratory features are presented. Neurological manifestations

included epilepsy, dementia and parkinsonism. Discussion

focuses on the distinction of this entity from the small

pallidal calcifications and on the pathophysiology of basal

ganglia mineralisation, in view of recent reports.

13. Bernstein Goral, H.; Bregman, B. S. Axotomized rubrospinal

neurons rescued by fetal spinal cord transplants maintain axon

collaterals to rostral CNS targets. Exp-Neurol. 1997 Nov;

148(1): 13-25; ISSN: 0014-4886.

UNITED-STATES. Neurons that maintain extensive axon

collaterals proximal to the site of axotomy may be better able

to survive injury. Early lesions of the rubrospinal tract lead to

retrograde cell death of the majority of axotomized immature

neurons. Transplants of fetal spinal cord tissue rescue

axotomized rubrospinal neurons and promote their axonal

regeneration. Rubrospinal neurons develop many of their axon

collaterals postnatally. The present study tests the hypothesis

that the axotomized rubrospinal neurons that are rescued by

transplants and regenerate their axons are those neurons that

have established axon collaterals to targets rostral to the

lesion. Neonatal rats received a transplant of fetal spinal cord

tissue placed into a midthoracic spinal cord hemisection. One

month after transplantation, the retrogradely transported

fluorescent tracers fast blue (FB) and diamidino yellow (DY)

were used to identify rubrospinal neurons with collaterals to

particular targets. FB was injected either into the

interpositus nucleus of the cerebellum or into the gray matter

of the cervical enlargement to identify collaterals to these

targets, and DY was injected into the spinal cord

approximately 5 mm caudal to the transplant and lesion site to

label retrogradely the neurons that regenerated their axons.

Double labeling was observed in the axotomized neurons of the

red nucleus after tracer injections into the cervical spinal

cord but not after injections into the cerebellum. This labeling

pattern indicates that axotomized rubrospinal neurons that are

rescued and regenerate axons caudal to the transplant

maintain axon collaterals at cervical spinal cord levels.

Cerebellar collaterals do not appear to play a role in the

survival and regrowth of axotomized rubrospinal neurons.. 0.

14. Blumenthal, D. T.; Shanske, S.; Schochet, S. S.; Santorelli, F. M.;

DiMauro, S.; Jaynesm, M.; Bodensteiner, J. Myoclonus epilepsy

with ragged red fibers and multiple mtDNA deletions.

Neurology. 1998 Feb; 50(2): 524-5; ISSN: 0028-3878.

UNITED-STATES. In a patient with clinical features of

myoclonus epilepsy with ragged red fibers (MERRF), molecular

genetic analysis of mitochondrial DNA did not show either of

the two point mutations typically associated with MERRF but

did show multiple deletions by Southern blot. This case further

illustrates the heterogeneity observed with mtDNA mutations..

EC 1.-; EC 1.3.99.1; EC 1.6.99.3; EC 1.9.3.1; EC 4.1.3.7; 0.

15. Bosco, G.; Rankin, A.; Poppele, R. Representation of passive

hindlimb postures in cat spinocerebellar activity. J-

Neurophysiol. 1996 Aug; 76(2): 715-26; ISSN: 0022-3077.

UNITED-STATES. 1. We report here about the modulation of

dorsal spinocerebellar tract (DSCT) activity by limb posture.

In principle, DSCT activity could represent limb position in one

of several ways. According to a classical notion of DSCT

function, DSCT activity might be expected to correlate with

changes in individual joint angles. However, given the evidence

for extensive polysynaptic convergence onto DSCT units, it is

reasonable to propose that DSCT activity represents more

global variables such as the orientation of limb segments or

the length and orientation of the whole limb. 2. In six

anesthetized cats we recorded the activity of 96

antidromically identified DSCT neurons while a robot arm

passively positioned the left hindfoot in 20 positions

distributed in the sagittal plane, holding each position for 8 s.

For each position we measured the joint angles, limb segment

angles, and the length and orientation of the limb axis (defined

as the line connecting the hip joint to the hindpaw). We used

regression statistics to quantify 1) possible relationships

among geometric variables of the hindlimb and 2)

relationships between DSCT firing rate and limb variables. 3.

First, we found a statistically significant relationship among

the joint angles that could be described by a covariance plane

accounting for approximately 70 percent of the total variance.

Thus the 3 degrees of freedom represented by the joint angles

in the sagittal plane are effectively reduced to only 2 by the

coupling between joints. This finding resembles that described

for the behaving cat during stance. However, the correlation

between the hip and ankle angles in the passively displaced

hindlimb was just the opposite of that observed during active

stance. Moreover, we observed that the length and the

orientation of the limb axis is determined simply by a linear

combination of the three joint angles. 4. Most of the DSCT

neurons (82 of 96) were significantly modulated by changes in

foot position (1-way analysis of variance, P < 0.001). For those

cells, we explored systematically how their activity was

related to limb geometric variables. We found mostly linear

relationships between individual joint or limb segments

angles and DSCT firing rates. However, although these

relationships were statistically significant, the random

variance was often quite high. Moreover, approximately 70% of

the cells were modulated by more than one joint or limb

segment angle, suggesting that a model incorporating global

geometric variables might explain a larger fraction of the

variance in the neural data. 5. Consequently we tested how

well DSCT activity was modulated by the length and the

orientation of the limb axis with the use of a linear regression

model with length and orientation (or the equivalent linear

combination of joint angles) as predictors. We found that this

model explained a larger fraction of the variability in the

firing pattern of nearly every modulated cell than did any of

the single joint models tested. 6. We also attempted to

account for the effect of the mechanical joint covariance on

this result by accounting for correlated independent variables

in the analysis. We used a regression model incorporating all

three joint or limb segment angles and performed a backward

elimination of insignificant or redundant variables. The result

was that 67% of the neurons were independently modulated by

at least two joint angles, indicating that the modulation did

not necessarily reflect the biomechanical constraint of joint

angle covariation, but rather a central convergence of sensory

information from more than a single joint. 7. From these

results we conclude that the firing rates of a majority of

DSCT neurons encode the position of the hindfoot relative to

the hip joint.(ABSTRACT TRUNCATED).

16. Brook, G. A.; Spitzer, C.; Nacimiento, W.; Woodhams, P. L.; Noth, J.

A novel early component of the cell body response in

axotomized Clarke's nucleus neurons revealed by monoclonal

antibody Py. Exp-Neurol. 1998 Jan; 149(1): 64-72; ISSN: 0014-

4886.

UNITED-STATES. The monoclonal antibody Py was initially

developed as a tool for the identification of subpopulations of

hippocampal neurons. Recently it has also been demonstrated

to be a useful marker for other populations of midbrain and

spinal cord neurons in which the antigen showed a strong

colocalization with cytoskeletal elements. To assess the

possible usefulness of Py as a tool for studying lesion-induced

cell body changes, densitometric analysis of altered Py-

immunoreactivity (Py-IR) has been compared with that of

microtubule-associated protein 2 (MAP2) in Clarke's nucleus

following axotomy. One week after a unilateral transection of

the dorsal spinocerebellar tract at Th9-10, Py-IR in the

Clarke's nucleus ipsilateral and caudal to the lesion was

reduced by approximately 40%. By 21 days, Py-IR was reduced

by approximately 50% (a near maximal reduction) and remained

constant up to 5 months after the lesion (the longest survival

time studied). Alterations of MAP2-IR in Clarke's nucleus were

later in onset, slower to develop, and less marked. The

differential distribution of the Py antigen in the CNS and its

rapid and long lasting loss indicate that the Py antibody is a

sensitive tool for studying novel early alterations of the

cytoskeleton which may be important molecular events in

axotomy-induced pathological processes.. 0; 0.

17. Buffo, A.; Holtmaat, A. J.; Savio, T.; Verbeek, J. S.; Oberdick, J.;

Oestreicher, A. B.; Gispen, W. H.; Verhaagen, J.; Rossi, F.;

Strata, P. Targeted overexpression of the neurite growth-

associated protein B-50/GAP-43 in cerebellar Purkinje cells

induces sprouting after axotomy but not axon regeneration into

growth-permissive transplants. J-Neurosci. 1997 Nov 15;

17(22): 8778-91; ISSN: 0270-6474.

UNITED-STATES. B-50/GAP-43 is a nervous tissue-specific

protein, the expression of which is associated with axon

growth and regeneration. Its overexpression in transgenic mice

produces spontaneous axonal sprouting and enhances induced

remodeling in several neuron populations (; ). We examined the

capacity of this protein to increase the regenerative potential

of injured adult central axons, by inducing targeted B-50/GAP-

43 overexpression in Purkinje cells, which normally show poor

regenerative capabilities. Thus, transgenic mice were

produced in which B-50/GAP-43 overexpression was driven by

the Purkinje cell-specific L7 promoter. Uninjured transgenic

Purkinje cells displayed normal morphology, indicating that

transgene expression does not modify the normal phenotype of

these neurons. By contrast, after axotomy numerous transgenic

Purkinje cells exhibited profuse sprouting along the axon and

at its severed end. Nevertheless, despite these growth

phenomena, which never occurred in wild-type mice, the

severed transgenic axons were not able to regenerate, either

spontaneously or into embryonic neural or Schwann cell grafts

placed into the lesion site. Finally, although only a moderate

Purkinje cell loss occurred in wild-type cerebella after

axotomy, a considerable number of injured transgenic neurons

degenerated, but they could be partially rescued by the

different transplants placed into the lesion site. Thus, B-

50/GAP-43 overexpression substantially modifies Purkinje

cell response to axotomy, by inducing growth processes and

decreasing their resistance to injury. However, the presence of

this protein is not sufficient to enable these neurons to

accomplish a full program of axon regeneration.. 0.

18. Cai, C.; Oakes, W. J. Hindbrain herniation syndromes: the Chiari

malformations (I and II). Semin-Pediatr-Neurol. 1997 Sep;

4(3): 179-91; ISSN: 1071-9091.

UNITED-STATES. Hindbrain hernias with or without

hydrosyringomyelia were difficult diagnostic problems before

the availability of magnetic resonance imaging. Today, the

problem seems not to be in evaluating the anatomical extent of

the caudal herniation of the cerebellum, but in determining

which patient should be considered for operative intervention

and the extent of the surgery. Chiari I patients are presenting

at younger ages, occasionally with irritability as their only

symptom. Should all of these children be submitted to an

operation? Chiari II patients are now operated on with the

first detectable symptom or evidence of a syrinx, and yet

medullary dysfunction from the Chiari II malformation

remains the leading cause of death in treated

myelomeningoceles today. Our knowledge of the natural history

of the untreated conditions and the increased safety of the

operation has made surgical intervention a much more viable

option for this group of patients.

19. Cardo, E.; Campistol, J.; Kirkham, F. [The role of resistance to C

active protein (R-APC) in a pediatric stroke]. Papel de la

resistencia a la proteina C activada (R-PCA) en el ictus

pediatrico. Rev-Neurol. 1997 Oct; 25(146): 1589-91; ISSN:

0210-0010.

SPAIN. INTRODUCTION: Activated protein C resistance is a

recently identified thrombophylic state which results from a

mutation in the factor V gene and has been shown to be an

important risk factor for peripheral venous thrombosis. We

report a case of paediatric stroke in whom we have identified

APC resistance. CLINICAL CASE: A boy presented acutely at the

age of 6 years with a severe right sided headache, vomiting,

unsteadiness and drowsiness which worsened over a period of

40 hours. Prior to this episode, he was neurologically and

developmentally normal except for occasional headaches. CT

showed low attenuation in the left cerebellar hemisphere, and

occipital lobe associated with acute hydrocephalus. Excision

biopsy of the left cerebellar cortex revealed inflammation and

possible infarction. Although he remained in a 'locked-in' state

with a flaccid quadriparesis for six months, he improved and

was left with a left side hemiplegia, multiple cranial nerve

palsies and a visual field defect. He represented at the age of

thirteen years with transient ischaemic attacks and was found

be heterozygous for the factor V Leiden mutation. Since he has

been warfarinised, his symptoms have improved. CONCLUSIONS:

Although cerebellar stroke in childhood is rare, it has been

underdiagnosed in the past. As recurrence is common, patients

should be fully investigated and followed up long term.

Screening for new factor such as APC-resistance is

recommended.. 0; 0; 81-81-2; 9001-24-5.

20. Cavanagh, J. B.; Holton, J. L.; Nolan, C. C. Selective damage to the

cerebellar vermis in chronic alcoholism: a contribution from

neurotoxicology to an old problem of selective vulnerability.

Neuropathol-Appl-Neurobiol. 1997 Oct; 23(5): 355-63; ISSN:

0305-1846.

ENGLAND. The curiously consistent localization of cerebellar

cortical damage in chronic alcoholism is re-evaluated in the

light of selective damage, with a similar topography in the

cerebellar vermal region, in superficial siderosis in man and in

experimental animals exposed to certain toxic substances.

Attention is drawn to the capacity for Purkinje cell dendrites

and Bergmann glia to extract materials from the CSF, and to

the close anatomical relationships of the susceptible lobules

I-II, IX and X to the roof of the IVth ventricle and to the

cistern of the great cerebral veins. This restriction of damage

to vermis and paravermis may reflect some

compartmentalization of CSF flow within leptomeninges,

consistently increasing exposure of these cerebellar surfaces

to materials circulating in the CSF. In other circumstances

when this pattern of damage is encountered it raises the

question as to whether other environmental agents, gaining

access to the CSF, may be similarly distributed.. 0; 0; 0;

16676-91-8; 304-21-2; 37203-49-9; 77-10-1; 83-74-9.

21. Ceccatelli, S.; Ahlbom, E.; Diana, A.; Zhivotovsky, B. Apoptosis in

rat hippocampal dentate gyrus after intraventricular

colchicine. Neuroreport. 1997 Dec 1; 8(17): 3779-83; ISSN:

0959-4965.

ENGLAND. The aim of this study was to examine the

neurodegenerative effects of intraventricular colchicine on

granule cells of the hippocampal dentate gyrus and to

characterise the modality of neuronal cell death. Male

Sprague-Dawley rats were killed 24 hours after a single

injection of colchicine into the third ventricle and nuclear

morphology, DNA single strand breaks and high molecular

weight DNA fragments were analysed to discriminate necrotic

from apoptotic cell death. In situ detection of fragmented DNA

was performed also on cerebellar sections. The results show

that dentate granule cells and cerebellar neurons in the

granule cell layer are vulnerable to colchicine administered

intraventricularly and that the affected neurons undergo

apoptosis.. 64-86-8.

22. Cerrito, F.; Aloisi, G.; Arminio, P.; Fanini, D. A new GABA-A

receptor subtype coupled with Ca++/Cl- synporter modulates

aminergic release from rat brain neuron terminals. J-

Neurosci-Res. 1998 Jan 1; 51(1): 15-22; ISSN: 0360-4012.

UNITED-STATES. The aim of the present study was to give a

better characterization of GABA receptors that modulate

aminergic release. GABA or muscimol (15 microM) increased

basal noradrenaline (3H-NA) release but reduced the following

K+-evoked 3H-NA release in the synaptosomes from rat

cerebellar cortex. Bicuculline and picrotoxin counteracted

these two effects. The same GABA modulation resulted to

operate also on dopaminergic and serotoninergic neuron

terminals. The increased basal noradrenaline release resulted

to be both calcium and chloride dependent and associated with

an increased entry of 45Ca++ into the synaptosomes. We

therefore advance the hypothesis of an involvement of a Cl-

/Ca++ synporter system coupled to the receptor. Baclofen also

reduced the K+-evoked 3H-NA release, but did not increase

basal 3H-NA release; moreover, the interaction of baclofen G

with GABA-B receptors resulted to be associated with the

inhibition of 45Ca++ entry into synaptosomes. GABA-B

receptors resulted to be present also on serotoninergic but not

on dopaminergic neuron terminals. The GABA-C receptor

agonist cis-4-aminocrotonic acid (CACA) did not influence

either basal or K+-evoked 3H-NA release. These results point

to a new type of GABA functional role through a different A-

family receptor subtype, coupled with calcium influx in

aminergic neuron terminals, modulating aminergic release.. 0;

0; 0; 51-41-2; 56-12-2; 7440-09-7; 7440-70-2.

23. Chang, H. M.; Linn, F. H.; Caplan, L. R. Bilateral anterior inferior

cerebellar artery territory infarcts. J-Neuroimaging. 1998 Jan;

8(1): 42-4; ISSN: 1051-2284.

UNITED-STATES. Bilateral anterior inferior cerebellar artery

(AICA) territory infarcts are rare. Their occurrence usually

signifies severe intracranial vertebrobasilar disease. Unlike

head computed tomography, magnetic resonance (MR) imaging

reveals these infarcts clearly and MR angiography allows the

intracranial vasculature to be defined noninvasively. We now

report a patient with bilateral AICA territory infarcts.

24. Chen, C.; Regehr, W. G. The mechanism of cAMP-mediated

enhancement at a cerebellar synapse. J-Neurosci. 1997 Nov 15;

17(22): 8687-94; ISSN: 0270-6474.

UNITED-STATES. Increases in cAMP have been shown

previously to enhance the strength of the granule cell to

Purkinje cell synapse. We have examined the mechanisms

underlying this enhancement in rat cerebellar brain slices.

Elevation of cAMP levels by forskolin increased synaptic

currents in a dose-dependent manner. Fluorometric calcium

measurements revealed that forskolin did not affect

presynaptic calcium influx or resting calcium levels. The

waveform of the presynaptic volley was also unaltered,

indicating that changes in the presynaptic action potential did

not contribute to synaptic enhancement. However, forskolin

enhanced the frequency but not the size of spontaneous

miniature EPSCs. There was a one-to-one correspondence

between increases of spontaneous and evoked

neurotransmitter release. These results suggest that forskolin

increases release at this synapse via presynaptic mechanisms

that do not alter calcium influx. The effect of forskolin on

paired-pulse facilitation was examined to assess the relative

contributions of changes in the probability of release (p) and

changes in the number of functional release sites (n) to this

form of enhancement. These experiments suggest that although

small changes in n cannot be excluded, most of the

enhancement arises from increases in p.. 60-92-4; 66428-89-

5; 7440-70-2.

25. Chen, W. Y.; Wang, J. J.; Yu, Q. X. [Effects of dorsal raphe

stimulation on activities of cerebellar nuclear neurons in the

rat]. Sheng-Li-Hsueh-Pao. 1996 Apr; 48(2): 132-40; ISSN:

0371-0874.

CHINA. The effects of stimulating dorsal raphe nucleus (DR) on

activities of three deep cerebellar nuclei (DCN) (medial,

interposed and lateral nuclei) were investigated. The results

were as follows: (1) Stimulation of DR elicited three types of

responses, inhibition, excitation, and biphasic response

(excitation-inhibition or inhibition-excitation) from DCN cells

with responsive latencies ranging from 10 to 84 ms. The

majority of responsive cells showed an inhibitory response

(76%-90%) with a latency less than 30 ms. (2) The spontaneous

discharge frequencies of the DCN cells were 5 to 120 Hz. The

cells with higher spontaneous discharge frequencies showed

low responsive rates to the DR stimulation, as compared with

lower firing frequency cells. (3) The depressive effect of DR

stimulation could be blocked by injection of 5-HT2/1c

antagonist methysergide (66.7%-83.3%). These results suggest

that raphe-cerbellum serotonergic afferent fibers may be

involved in the cerebellar sensorimotor integration process by

exerting some modulatory effects on the DCN cell's activities..

50-67-9.

26. Chu, H. P.; Etgen, A. M. A potential role of cyclic GMP in the

regulation of lordosis behavior of female rats. Horm-Behav.

1997 Oct; 32(2): 125-32; ISSN: 0018-506X.

UNITED-STATES. Nitric oxide (NO) has been suggested to play a

crucial role in the regulation of lordosis behavior via

stimulation of guanylyl cyclase to synthesize cyclic GMP.

Whalen and Lauber (1986, Neurosci. Biobehav. Rev. 10, 47-53)

hypothesized that hormones and pharmacological agents known

to facilitate lordosis in estrogen-primed rodents act through

cyclic GMP. The compound 1H-[1,2, 4]oxadiazolo[4,3-

a]quinoxalin-1-one (ODQ) has been shown to selectively inhibit

NO-stimulated cyclic GMP production. In the present study, we

investigated the effects of ODQ on lordosis behavior. Female

rats were implanted with a guide cannula aimed at the lateral

or third ventricles by stereotaxic surgery, and their ovaries

were bilaterally removed. Five days later, animals were

injected subcutaneously with 2 microg estradiol benzoate at

48 and 24 hr, and 200 microg progesterone 4 hr before

behavioral testing. ODQ or vehicle (1 microl) was administered

at the time of progesterone treatment or 20 min before

lordosis testing. ODQ significantly decreased lordosis

quotients and the quality of lordosis at both intervals of drug

infusion. Locomotor activities, measured by line crossing and

rearing, were not affected by ODQ. ODQ also inhibited cyclic

GMP accumulation in response to NMDA stimulation in

hypothalamic and cerebellar slices in vitro. We conclude that

cyclic GMP produced by NO generation is an important

modulator of female rat sexual behavior. Copyright 1997

Academic Press.. 0; 0; 0; 0; 10102-43-9; 7665-99-8.

27. Comu, S.; Weng, W.; Olinsky, S.; Ishwad, P.; Mi, Z.; Hempel, J.;

Watkins, S.; Lagenaur, C. F.; Narayanan, V. The murine P84

neural adhesion molecule is SHPS-1, a member of the

phosphatase-binding protein family. J-Neurosci. 1997 Nov 15;

17(22): 8702-10; ISSN: 0270-6474.

UNITED-STATES. P84 is a neuronal membrane glycoprotein

that promotes the attachment and neurite outgrowth of

cultured murine cerebellar cells. The heterophilic adhesive

properties of P84 and its localization at sites of

synaptogenesis suggest that it may be involved in regulation

of synapse formation or maintenance. P84 is expressed in

subsets of neurons throughout the CNS. By cloning the cDNA

encoding murine P84, we have discovered that this molecule is

a member of a family of phosphatase-binding proteins and is

identical to the murine SHPS-1 cDNA. Here we report the

cloning of two alternatively spliced forms of P84 and describe

its localization within the CNS by in situ hybridization.. EC

3.1.3; 0; 0; 0; 0; 0.

28. Coplin, W. M.; Kim, D. K.; Kliot, M.; Bird, T. D. Mutism in an adult

following hypertensive cerebellar hemorrhage: nosological

discussion and illustrative case. Brain-Lang. 1997 Oct 1;

59(3): 473-93; ISSN: 0093-934X.

UNITED-STATES. Mutism after cerebellar injury has been

associated with tumors, hemorrhage, and surgery of midline

cerebellar structures. Literature review identified 54 cases,

primarily in children after surgical splitting of the inferior

vermis. We present a 47-year-old who developed transient

mutism after cerebellar hemorrhage. This represents the first

report of transient mutism in an adult with neither tumor nor

brainstem infarction and documents the importance of

cerebellar structures for initiation and production of speech in

adulthood. This case further differs from those previous

because of the long mute period and the subsequent return of

continued ataxic and dysarthric speech.

29. Cosi, C.; Suzuki, H.; Skaper, S. D.; Milani, D.; Facci, L.; Menegazzi,

M.; Vantini, G.; Kanai, Y.; Degryse, A.; Colpaert, F.; Koek, W.;

Marien, M. R. Poly(ADP-ribose) polymerase (PARP) revisited. A

new role for an old enzyme: PARP involvement in

neurodegeneration and PARP inhibitors as possible

neuroprotective agents. Ann-N-Y-Acad-Sci. 1997 Oct 15; 825:

366-79; ISSN: 0077-8923.

UNITED-STATES. EC 2.4.2.30; 0; 0; 0; 0; 0; 0; 0; 27208-38-4;

28289-54-5; 51-61-6; 56-86-0; 65-85-0.

30. Couldwell, W. T.; Zhang, W.; Allen, R.; Arce, D.; Stillerman, C. B.

Cerebellar contusion associated with type I Chiari

malformation following supratentorial head trauma: case

report. Neurol-Res. 1998 Jan; 20(1): 93-6; ISSN: 0161-6412.

ENGLAND. Acute presentation of Type I Chiari malformation in

children is distinctly rare. An 11 year old male suffered a

trauma to the right temporal-parietal region in a tobogganing

accident resulting in an open depressed skull fracture.

Radiographic evaluation included a Computed Tomographic scan

which also demonstrated a significant cerebellar contusion

and the presence of subarachnoid hemorrhage in the region of

craniovertebral junction. Magnetic Resonance imaging revealed

an underlying Type I Chiari malformation. Somatosensory

evoked responses shortly following the injury demonstrated

slowing of conduction across the lower brainstem. The open

depressed fracture was debrided and elevated. Subsequent

observation resulted in slow improvement in neurological

function. A followup somatosensory evoked potential study

performed 21 days following the accident showed

improvement in conduction across the craniovertebral

junction. The tonsillar ectopia associated with Type I Chiari

malformation may predispose to cerebellar, upper spinal and

brainstem injury following supratentorial trauma.

31. Crawford, J. S.; Konkol, R. J. Familial hemiplegic migraine with

crossed cerebellar diaschisis and unilateral meningeal

enhancement. Headache. 1997 Oct; 37(9): 590-3; ISSN: 0017-

8748.

UNITED-STATES. A 6-year-old boy with a family history of

hemiplegic migraine had a hemiplegic migraine lasting for 6

days complicated by prolonged fever, lethargy, and two brief

focal seizures. An acute single photon emission computerized

tomogram (SPECT) demonstrated decreased blood flow in the

symptomatic cerebral hemisphere as well as crossed

cerebellar diaschisis not previously documented in migraine.

Another unique finding was the MRI with enhancement of the

meninges and pial vessels over the symptomatic cerebral

hemisphere. These findings suggest cerebellar and extra-axial

involvement as components of hemiplegic migraine.. 7440-54-

2.

32. Crivello, F.; Tzourio, N.; Poline, J. B.; Woods, R. P.; Mazziotta, J. C.;

Mazoyer, B. Intersubject variability in functional

neuroanatomy of silent verb generation: assessment by a new

activation detection algorithm based on amplitude and size

information. Neuroimage. 1995 Dec; 2(4): 253-63; ISSN: 1053-

8119.

UNITED-STATES. We present an experimental evaluation of a

new algorithm for the detection of activated areas in brain

functional maps. The new algorithm, named HMSD, is based on a

hierarchical multiscale description of the difference image in

terms of connected objects. Size and magnitude of each object

are simultaneously tested with respect to a bidimensional

frequency distribution derived using Monte-Carlo simulations

under the null hypothesis. In the present work. HMSD was

applied to the analysis of a silent verb generation PET

activation protocol conducted in six right-handed subjects.

Applied to single-subject data. HMSD reveals activation

located in the left inferior frontal gyrus in three subjects

(two in the pars opercularis, one in the pars triangularis), and

in the pars opercularis of the right inferior frontal gyrus in

one case, the latter being combined to a crossed cerebellar

activation. Overall, single-case results were consistent with

the analyses of stereotactically averaged data. Despite a 2D

implentation. HMSD detection performances of averaged data

were better than that obtained with the 2D version of

statistical parametric mapping (SPM) and comparable to that

of the 3D version of SPM.

33. Cruz Martinez, A.; Palau, F. Central motor conduction time by

magnetic stimulation of the cortex and peripheral nerve

conduction follow-up studies in Friedreich's ataxia.

Electroencephalogr-Clin-Neurophysiol. 1997 Dec; 105(6): 458-

61; ISSN: 0013-4694.

IRELAND. A follow-up clinical study, peripheral motor and

sensory nerve conduction velocities and central motor

conduction by magnetic stimulation of the cortex were

performed in 13 patients with classical Friedreich's ataxia

(FA) phenotype, for a period of 9-12 years. Clinical worsening

was unrelated to peripheral nerve abnormalities. The

amplitude of the nerve action potentials and delayed

conduction velocity remained unchanged for several years.

Central motor conduction times were abnormal in all patients.

Clinical conditions worsened significantly between successive

examinations with significant increments in threshold and

significant decrement of the amplitude of motor evoked

potentials. The results are consistent with progressive

pyramidal and cerebellar pathways involvement as the cause

of clinical worsening in FA.

34. Cuadros, M. A.; Rodriguez Ruiz, J.; Calvente, R.; Almendros, A.;

Marin Teva, J. L.; Navascues, J. Microglia development in the

quail cerebellum. J-Comp-Neurol. 1997 Dec 22; 389(3): 390-

401; ISSN: 0021-9967.

UNITED-STATES. We used the QH1 antibody to study changes in

the morphological features and distribution of microglial cells

throughout development in the quail cerebellum. Few

microglial precursors were present in the cerebellar anlage

before the ninth incubation day (E9), whereas many precursors

apparently entered the cerebellum from the meninges in the

basal region of the cerebellar peduncles between E9 and E16.

From this point of entry into the nervous parenchyma, they

spread through the cerebellar white matter, forming a 'stream'

of labeled cells that could be seen until hatching (E16). The

number of microglial cells in the cerebellar cortex increased

during the last days of embryonic life and first posthatching

week, whereas microglial density within the white matter

decreased after hatching. As a consequence, the differences in

microglial cell density observed in the cerebellar cortex and

the white matter during embryonic life diminished after

hatching, and microglia showed a nearly homogeneous pattern

of distribution in adult cerebella. Ameboid and poorly ramified

microglial cells were found in developing stages, whereas only

mature microglia appeared in adult cerebella. Our observations

suggest that microglial precursors enter the cerebellar anlage

mainly by traversing the pial surface at the basal region of the

peduncles, then migrate along the white matter, and finally

move radially to the different cortical layers. Differentiation

occurs after the microglial cells have reached their final

position. In other brain regions the development of microglia

follows similar stages, suggesting that these steps are

general rules of microglial development in the central nervous

system.

35. Czerny, C.; Rand, T.; Gstoettner, W.; Woelfl, G.; Imhof, H.; Trattnig,

S. MR imaging of the inner ear and cerebellopontine angle:

comparison of three-dimensional and two-dimensional

sequences. AJR-Am-J-Roentgenol. 1998 Mar; 170(3): 791-6;

ISSN: 0361-803X.

UNITED-STATES. OBJECTIVE: The aim of the study was to

compare the ability of three-dimensional (3D) T2-weighted

turbo spin-echo and gadolinium-enhanced 3D T1-weighted

gradient-echo sequences with two-dimensional (2D) T2-

weighted turbo spin-echo and gadolinium-enhanced T1-

weighted spin-echo sequences to reveal anatomic and

pathologic structures of the inner ear and cerebellopontine

angle. SUBJECTS AND METHODS: Thirty-one patients underwent

axial 2D T2-weighted turbo spin-echo and 3D T2-weighted

turbo spin-echo MR imaging, axial and coronal 2D T1-weighted

spin-echo MR imaging before and after i.v. injection of

gadopentetate dimeglumine, and gadolinium-enhanced axial 3D

T1-weighted gradient-echo MR imaging. The visualization of

anatomic and pathologic structures on the different sequences

was evaluated. Statistical analysis was performed from the

data obtained from the visual evaluation of the anatomic

structures on the different sequences. Signal-to-noise and

contrast-to-noise ratios were calculated for the gadolinium-

enhanced 3D T1-weighted gradient-echo and 2D T1-weighted

spin-echo sequences, and statistical evaluation was

performed. RESULTS: The 3D sequences enabled excellent

visualization of 94% of all evaluated anatomic structures, and

the 2D sequences enabled excellent visualization in only 3% of

these structures. Pathologic structures were revealed in all

cases by one or both of the 3D sequences. Diagnosis in all

patients could be made by using the combination of the 3D T2-

weighted turbo spin-echo and the gadolinium-enhanced 3D T1-

weighted gradient-echo sequences. However, the 2D sequences

failed to show pathologic structures in three patients. We

found a significant statistical difference for the visualization

of anatomic structures with the 3D and 2D sequences (p <

.0001) and no significant statistical difference for the signal-

to-noise and contrast-to-noise ratios with the 3D T1-

weighted gradient-echo and 2D T1-weighted spin-echo

sequences. CONCLUSION: The 3D sequences revealed anatomic

structures significantly better than did the 2D sequences and

showed pathologic structures considerably more often than did

the 2D sequences in all patients. MR imaging of the inner ear

and cerebellopontine angle performed with 3D T2-weighted

turbo spin-echo and gadolinium-enhanced 3D T1-weighted

gradient-echo sequences provided the most accurate imaging

leading to diagnosis in cases of abnormality.. 0; 80529-93-7.

36. Czerny, C.; Trattnig, S.; Baumgartner, W. D.; Gstottner, W.; Imhof,

H. [MRI of the regions of the inner ear and cerebellopontine

angle using a 3D T2-weighted turbo spin-echo sequence.

Comparison with conventional 2D T2-weighted turbo spin-echo

sequences and T1-weighted spin-echo sequences]. MRT der

Innenohr- und Kleinhirnbruckenwinkelregion mit einer 3D T2-

gewichteten Turbo-Spin-Echo-Sequenz. Vergleich mit

konventionellen 2D T2-gewichteten Turbo-Spin-Echo-

Sequenzen und T1-gewichteten Spin-Echo-Sequenzen. Rofo-

Fortschr-Geb-Rontgenstr-Neuen-Bildgeb-Verfahr. 1997 Oct;

167(4): 377-83; ISSN: 0936-6652.

GERMANY. PURPOSE: To assess the value of a three-

dimensional (3D) T2-weighted turbo spin-echo sequence (3D

T2-TSE) in comparison to conventional two-dimensional (2D)

T2-weighted TSE and unenhanced and enhanced T1-weighted

spin-echo sequences (SE) in imaging anatomic structures and

pathologic changes of the inner ear and cerebellopontine angle.

PATIENTS AND METHODS: The inner ear and cerebellopontine

angle were investigated by MRI in three healthy volunteers and

18 patients performing a 2D T2-weighted turbo spin-echo

sequence and a 3D T2-TSE in the axial plane. In the patient

study, 2D T1-weighted SE sequences both before and after the

i.v. injection of gadopentetate dimeglumine in both the axial

and coronal plane were performed in addition. RESULTS: Only

the 3D T2-TSE enabled an accurate imaging of the anatomic

structures. In cases of pathology, the 3D T2-TSE provided

additional information to the performed 2D sequences. The

combination of the 3D T2-TSE with unenhanced and enhanced

2D T1-weighted SE enabled the most accurate diagnosis in

cases of pathology. CONCLUSIONS: Accurate depiction of

anatomic structures of the inner ear and cerebellopontine

angle could be obtained by 3D T2-TSE only. The most accurate

diagnosis in cases of pathology was provided by the

combination of the 3D T2-TSE with unenhanced and enhanced

2D T1-weighted spin-echo sequences.. 80529-93-7.

37. Desmond, J. E.; Gabrieli, J. D.; Wagner, A. D.; Ginier, B. L.; Glover, G.

H. Lobular patterns of cerebellar activation in verbal working-

memory and finger-tapping tasks as revealed by functional

MRI. J-Neurosci. 1997 Dec 15; 17(24): 9675-85; ISSN: 0270-

6474.

UNITED-STATES. The lobular distributions of functional

activation of the cerebellum during verbal working-memory

and finger movement tasks were investigated using functional

magnetic resonance imaging (fMRI). Relative to a rest control,

finger tapping of the right hand produced ipsilateral-increased

activation in HIV/HV [Roman numeral designations based on

Larsell's () nomenclature] and HVI and weaker activation in

HVIII that was stronger on the ipsilateral side. For a working-

memory task, subjects were asked to remember six (high load)

or one (low load) visually presented letters across a brief

delay. To assess the motoric aspects of rehearsal in the

absence of working memory, we asked the subjects to

repeatedly read subvocally six or one letters at a rate that

approximated the internally generated rehearsal of working

memory (motoric rehearsal task). For both tasks, bilateral

regions of the superior cerebellar hemispheres (left superior

HVIIA and right HVI) and portions of posterior vermis (VI and

superior VIIA) exhibited increased activation during high

relative to low load conditions. In contrast, the right inferior

cerebellar hemisphere (HVIIB) exhibited this load effect only

during the working-memory task. We hypothesize that HVI and

superior HVIIA activation represents input from the

articulatory control system of working memory from the

frontal lobes and that HVIIB activation is derived from the

phonological store in temporal and parietal regions. From

these inputs, the cerebellum could compute the discrepancy

between actual and intended phonological rehearsal and use

this information to update a feedforward command to the

frontal lobes, thereby facilitating the phonological loop.

38. Dittman, J. S.; Regehr, W. G. Mechanism and kinetics of

heterosynaptic depression at a cerebellar synapse. J-Neurosci.

1997 Dec 1; 17(23): 9048-59; ISSN: 0270-6474.

UNITED-STATES. High levels of activity at a synapse can lead

to spillover of neurotransmitter from the synaptic cleft. This

extrasynaptic neurotransmitter can diffuse to neighboring

synapses and modulate transmission via presynaptic receptors.

We studied such modulation at the synapse between granule

cells and Purkinje cells in rat cerebellar slices. Brief tetanic

stimulation of granule cell parallel fibers activated inhibitory

neurons, leading to a transient elevation of extracellular

GABA, which in turn caused a short-lived heterosynaptic

depression of the parallel fiber to Purkinje cell EPSC.

Fluorometric calcium measurements revealed that this

synaptic inhibition was associated with a decrease in

presynaptic calcium influx. Heterosynaptic inhibition of

synaptic currents and calcium influx was eliminated by

antagonists of the GABAB receptor. The magnitude and time

course of the depression of calcium influx were mimicked by

the rapid release of an estimated 10 microM GABA using the

technique of flash photolysis. We found that inhibition of

presynaptic calcium influx peaked within 300 msec and

decayed in <3 sec at 32 degrees C. These results indicate that

presynaptic GABAB receptors can sense extrasynaptic GABA

increases of several micromolar and that they rapidly regulate

the release of neurotransmitter primarily by modulating

voltage-gated calcium channels.. 0; 0; 0; 0; 0; 56-12-2; 7440-

70-2.

39. Dollfus, H.; Joanny Flinois, O.; Doco Fenzy, M.; Veyre, L.; Joanny

Flinois, L.; Khoury, M.; Jonveaux, P.; Abitbol, M.; Dufier, J. L.

Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de

novo translocation. Am-J-Ophthalmol. 1998 Mar; 125(3): 397-

9; ISSN: 0002-9394.

UNITED-STATES. PURPOSE: To report a patient with a

phenotype suggestive of Gillespie syndrome and with a

chromosomal abnormality. METHODS: Clinical evaluation

showed bilateral superior coloboma, foveal hypoplasia, and

inferior cerebellar hypoplasia. Karyotyping as well as

investigation of the PAX6 gene were performed. RESULTS: The

karyotype of the patient disclosed a de novo translocation

t(X;11)(p22.32;p12). Fluorescent in situ hybridization and the

search for mutations excluded direct implication of the PAX6

gene. CONCLUSION: This is, to our knowledge, the first report

of a chromosomal abnormality detected in a patient with a

Gillespie syndrome phenotype.

40. Dunn, M. E.; Schilling, K.; Mugnaini, E. Development and fine

structure of murine Purkinje cells in dissociated cerebellar

cultures: neuronal polarity. Anat-Embryol-Berl. 1998 Jan;

197(1): 9-29; ISSN: 0340-2061.

GERMANY. Cerebellar Purkinje cells (PC) display a highly

distinctive form of polarity. We have cultured murine PCs from

dissociated E16 cerebellar anlagen for 1 week to investigate

the early stages of neuronal compartmentalization and

synaptic interactions, features which are important for the

establishment of neuronal polarity. To unequivocally identify

the PCs we utilized light and electron microscopic

immunocytochemistry with an anti-serum to the cell class-

specific marker L7/pcp2 gene product. The PCs typically show

a single, long axon, numerous short appendages classified as

filopodia and protospines, and a small number of

protodendrites. The nucleus is positioned asymmetrically in

both the horizontal and vertical axes of the soma. The Golgi

apparatus, coated and uncoated vesicles, and mitochondria are

prominent ultrastructural features, while the endoplasmic

reticulum is highly fragmented. The cell body receives

rudimentary synapses on its smooth surfaces and appendages

and no consistent morphological differences were detected

between these elementary contacts. The axon is clearly

identifiable; it emanates from either the cell body or a

protodendrite, bifurcates at predominantly right angles, forms

beaded collaterals, and terminates with relatively large

growth cones. The varicosities of the PC axon contain

pleomorphic synaptic vesicles and form rudimentary synapses

primarily with the dendritic shafts of immunonegative

neurons. The protodendrites are short, quickly tapering and

sparsely branched; they emit numerous filopodia and immature

spines and terminate with small growth cones. Rudimentary

synapses are received on the proximal dendritic shafts and

filopodia, and more mature synapses occur frequently on

protospines. With few exceptions, PCs lie atop an astrocytic

bed layer and glial processes are apposed to the various

aspects of the PC body left free by the afferent axons. By

contrast, PC processes are largely free of glial sheaths. We

conclude that the "stellate stage" of PC development in situ is

replicated rather faithfully in culture and that PCs have

established polarity and have begun to form intercellular

contacts by 1 week in vitro. Moreover, the PCs are already

morphologically distinct from other cell types in the 1 week

cultures, although they have yet to develop the differentiated

features that distinguish mature PCs.

41. Dunn, M. E.; Schilling, K.; Mugnaini, E. Development and fine

structure of murine Purkinje cells in dissociated cerebellar

cultures: dendritic differentiation, synaptic maturation, and

formation of cell-class specific features. Anat-Embryol-Berl.

1998 Jan; 197(1): 31-50; ISSN: 0340-2061.

GERMANY. The morphological differentiation of E16 murine

Purkinje cells (PCs) in dissociated cerebellar cultures was

analyzed by light and electron microscopic

immunocytochemistry after 2-5 weeks in vitro (wiv), with

particular emphasis on dendritic differentiation, synaptic

maturation, and formation of stereotypical fine structural

features. This study complements a companion paper on the

features of PCs after 1 wiv. After 2 wiv, the PCs have an

eccentric nucleus and the cytoplasmic organelles appear

immature; the axon has a distinct initial segment and beaded

axon collaterals but its boutons still contain sparse synaptic

vesicles; dendrites show few bifurcations and tufts of spiny

branchlets. After 3 wiv, the PCs display a centered nucleus, an

extensive hypolemmal cisternal system, and stacks of up to

four cisterns of granular endoplasmic reticulum; there is an

increased number of dendritic bifurcations, spiny branchlets,

mature spines, and axonal branches; dendritic tips still

contain vesicle clusters, suggesting growth, and many

synapses and afferent boutons continue to display immature

features. After 4 wiv, elaborate perinucleolar coiled body

rosettes, subsurface cistern-mitochondrion complexes and

large stacks of granular endoplasmic reticulum finally appear

within the soma; dendrites show a further increase in the

numbers of bifurcations, segments and spines; most spines are

synaptic and show mature features; afferent synapses are

differentially distributed; PC boutons consistently display

mature features and show a considerable degree of target

specificity, although naked spines and reduced glial sheaths

persist. After 5 wiv, PCs do not show further maturation and

some dystrophic features appear. We conclude that under

standard conditions and despite the disruption of normal

tissue organization, PCs in dissociated cultures differentiate

maximally after 4 wiv, at which stage they display many of

the light and electron microscopic features that characterize

mature PCs in situ. This prolonged developmental time-frame

resembles that in the normal cerebellum. In view of the

increasing usage of dissociated cerebellar cultures to study

aspects of neuronal differentiation, synaptic activation and

neuronal-glial interactions, an elucidation of the

neurocytology of dissociated cerebellar cultures as presented

in this study provides important clues for the interpretation

of experimental data.

42. el Mestikawy, S.; Wehrle, R.; Masson, J.; Lombard, M. C.; Hamon, M.;

Sotelo, C. Distribution pattern and ultrastructural localization

of Rxt1, an orphan Na+/Cl(-)-dependent transporter, in the

central nervous system of rats and mice. Neuroscience. 1997

Mar; 77(2): 319-33; ISSN: 0306-4522.

UNITED-STATES. The cellular and subcellular localization of

Rxt1 protein, an orphan Na+/Cl(-)-dependent transporter, was

investigated in the central nervous system of rats and mice,

with rabbit polyclonal antibodies specifically directed against

its C-terminal region. At the light microscope level, the

distribution of Rxt1, visualized by the immunoperoxidase

method, was found to be similar in rats and mice. Labelled

elements were present in numerous gray matter regions of the

central nervous system, from the olfactory bulb to the spinal

cord. In all labelled regions, immunoreactivity was confined to

the neuropil where both a diffuse labelling of low intensity

and an intense punctate staining were noted. To further

identify the nature of the cellular elements bearing the

punctate staining, possible changes in this labelling pattern

were investigated: (i) in deep cerebellar nuclei and lateral

vestibular nucleus of the Lurcher mutant mouse, in which all

cerebellar Purkinje cells are missing and (ii) in the rat

cervical spinal cord, 10 days after multiple resections of

dorsal roots. The vast majority of the punctate structures,

delineating the neuronal perikaryal and stem dendritic

contours, had disappeared in the mutant mouse, providing

evidence that they belong to Purkinje cell axon terminals. In

rhizotomized rats, the intense labelling in laminae I and III

had disappeared, demonstrating that it occurred in subclasses

of axonal projections of primary afferent fibres. These results

strongly suggest that Rxt1 is present in presynaptic axon

terminals. The electron microscopic study was carried out in

the hippocampus, cerebellum and lateral vestibular nucleus of

control mice, where Rxt1-labelled punctate structures were

found to be abundant. Immunostaining was confined to axon

terminals, particularly in hippocampal and cerebellar mossy

fibres and in Purkinje cell axonal terminations of the

cerebellar deep nuclei and lateral vestibular nucleus. In the

cerebellar cortex, axon terminals belonging to inhibitory local

circuit neurons (basket and Golgi cells), were free of labelling.

The observations reported in this study have shown that: (1)

The Rxt1 transporter is neuron-specific, and is expressed by

only some classes or even subclasses of neuronal systems. (2)

This transporter can be encountered in excitatory axons using

glutamate as neurotransmitter (hippocampal and cerebellar

mossy fibres: primary afferent fibres), as well as in inhibitory

axons known by their GABAergic nature (Purkinje cell axon

terminals) where it might be involved in the re-uptake process

of one or several molecules released from corresponding

terminals.. 0; 0; 0.

43. Erickson, S. L.; O'Shea, K. S.; Ghaboosi, N.; Loverro, L.; Frantz, G.;

Bauer, M.; Lu, L. H.; Moore, M. W. ErbB3 is required for normal

cerebellar and cardiac development: a comparison with ErbB2-

and heregulin-deficient mice. Development. 1997 Dec; 124(24):

4999-5011; ISSN: 0950-1991.

ENGLAND. Heregulins bind directly to ErbB3 and ErbB4

receptors, leading to multiple dimerization possibilities

including heterodimerization with the ErbB2 receptor. We have

generated ErbB3-, ErbB2- and heregulin-deficient mice to

assess their roles in development and differentiation.

Heregulin(-/-) and ErbB2(-/-) embryos died on E10.5 due to a

lack of cardiac ventricular myocyte differentiation; ErbB3(-/-

) embryos survived until E13.5 exhibiting cardiac cushion

abnormalities leading to blood reflux through defective valves.

In ErbB3(-/-) embryos, the midbrain/hindbrain region was

strikingly affected, with little differentiation of the

cerebellar plate. Cranial ganglia defects, while present in all

three nulls, were less severe in ErbB3(-/-) embryos. The

cranial ganglia defects, along with a dramatic reduction in

Schwann cells, enteric ganglia and adrenal chromaffin cells,

suggests a generalized effect on the neural crest. Numerous

organs, including the stomach and pancreas also exhibited

anomalous development.. EC 2.7.1.-; 0; 0; 0; 0; 0; 0; 0; 0.

44. Evanson, E. J.; Lewis, P. D.; Colquhoun, I. R. Primary germinoma of

the posterior cranial fossa: a case report. Neuroradiology.

1997 Oct; 39(10): 716-8; ISSN: 0028-3940.

GERMANY.

45. Faust, P. L.; Hatten, M. E. Targeted deletion of the PEX2

peroxisome assembly gene in mice provides a model for

Zellweger syndrome, a human neuronal migration disorder. J-

Cell-Biol. 1997 Dec 1; 139(5): 1293-305; ISSN: 0021-9525.

UNITED-STATES. Zellweger syndrome is a peroxisomal

biogenesis disorder that results in abnormal neuronal

migration in the central nervous system and severe neurologic

dysfunction. The pathogenesis of the multiple severe

anomalies associated with the disorders of peroxisome

biogenesis remains unknown. To study the relationship

between lack of peroxisomal function and organ dysfunction,

the PEX2 peroxisome assembly gene (formerly peroxisome

assembly factor-1) was disrupted by gene targeting.

Homozygous PEX2-deficient mice survive in utero but die

several hours after birth. The mutant animals do not feed and

are hypoactive and markedly hypotonic. The PEX2-deficient

mice lack normal peroxisomes but do assemble empty

peroxisome membrane ghosts. They display abnormal

peroxisomal biochemical parameters, including accumulations

of very long chain fatty acids in plasma and deficient

erythrocyte plasmalogens. Abnormal lipid storage is evident in

the adrenal cortex, with characteristic lamellar-lipid

inclusions. In the central nervous system of newborn mutant

mice there is disordered lamination in the cerebral cortex and

an increased cell density in the underlying white matter,

indicating an abnormality of neuronal migration. These

findings demonstrate that mice with a PEX2 gene deletion have

a peroxisomal disorder and provide an important model to

study the role of peroxisomal function in the pathogenesis of

this human disease.. 0; 0; 0; 135847-86-8.

46. Feske, S. K.; Sperling, R. A.; Schwartz, R. B. Extensive reversible

brain magnetic resonance lesions in a patient with HELLP

syndrome. J-Neuroimaging. 1997 Oct; 7(4): 247-50; ISSN:

1051-2284.

UNITED-STATES. A severe form of toxemia of pregnancy with

microangiopathic hemolytic anemia, elevated liver enzymes,

and low platelets has been called the HELLP syndrome. A

patient with the HELLP syndrome developed a severe,

reversible encephalopathy. Brain computed tomography and

magnetic resonance imaging showed abnormalities consistent

with edema limited to the posterior circulation territory. The

location of the lesions and their occurrence in the HELLP

syndrome support suggestions that the vulnerability of

posterior structures in eclamptic encephalopathy is due to a

vascular susceptibility of the posterior circulation and that

endothelial cell dysfunction plays an important role in the

pathogenesis of eclamptic encephalopathy.

47. Fu, Q. G.; Flament, D.; Coltz, J. D.; Ebner, T. J. Relationship of

cerebellar Purkinje cell simple spike discharge to movement

kinematics in the monkey. J-Neurophysiol. 1997 Jul; 78(1):

478-91; ISSN: 0022-3077.

UNITED-STATES. The simple spike discharge of 231 cerebellar

Purkinje cells in ipsilateral lobules V and VI was recorded in

three monkeys trained to perform a visually guided reaching

task requiring movements of different directions and

distances. The discharge of 179 cells was significantly

modulated during movement to one or more targets. Mean

simple spike rate was fitted to a cosine function for direction

tuning, a simple linear function for distance modulation, and a

multiple linear regression model that included terms for

direction, distance, and target position. On the basis of the fit

to the direction and distance models, there were more

distance-related than direction-related Purkinje cells. The

simple spike discharge of most direction-related cells

modulated at only one target distance. The preferred

directions for the simple spike tuning were not uniformly

distributed across the workspace. The discharge of most

distance-related cells modulated along only one movement

direction. On the basis of the multiple linear regression model,

simple spike discharge was also correlated with target

position, in addition to direction and distance. Approximately

half of the Purkinje cells had simple spike activity associated

with only a single parameter, and only a small fraction of the

cells with all three. The multiple regression model was

extended to evaluate the correlations as a function of time.

Considerable overlap occurred in the timing of the simple

spike correlations with the parameters. The latency for

correlation with movement direction occurred mainly in a

500-ms interval centered on movement onset. The correlations

with target position also occurred around movement onset, in

the range of -200-500 ms. Distance correlations were more

variable, with onset latencies from -500 to 1,000 ms. These

results demonstrate that the simple spike discharge of

cerebellar Purkinje cells is correlated with movement

direction, distance, and target position. Comparing these

results to motor cortical discharge shows that the

correlations with these parameters were weaker in Purkinje

cell simple spike discharge, and that, for the majority of

Purkinje cells, the simple spike discharge was significantly

related to only a single movement parameter. Other

differences between simple spike responses and those of

motor cortical cells include the nonuniform distribution of

preferred directions and the extensive overlap in the timing of

the correlations. These differences suggest that Purkinje cells

process, encode, and use kinematic information differently

than motor cortical neurons.

48. Fushiki, H.; Barmack, N. H. Topography and reciprocal activity of

cerebellar Purkinje cells in the uvula-nodulus modulated by

vestibular stimulation. J-Neurophysiol. 1997 Dec; 78(6): 3083-

94; ISSN: 0022-3077.

UNITED-STATES. In the rabbit uvula-nodulus, vestibular and

optokinetic information is mapped onto parasagittal zones by

climbing fibers. These zones are related functionally to

different pairs of vertical semicircular canals, otolithic

inputs and horizontal optokinetic inputs. Vestibular

stimulation restricted to one of these zones modulates

climbing fiber responses (CFRs). Within each of these zones,

simple spikes (SSs) are modulated reciprocally with CFRs. In

rabbits anesthetized with chloralose-urethan, we have used

vestibular and optokinetic stimulation to evoke CFRs within a

parasagittal zone while recording from Purkinje cells in

adjacent zones. We have examined whether the CFRs evoked by

vestibular stimulation in one zone influence the SSs of an

adjacent zone. CFRs and SSs were recorded during roll

vestibular stimulation. The orientation of the head of the

rabbit with respect to the axis of rotation was varied

systematically so that a climbing fiber null plane could be

determined. This null plane was the orientation of the head

about the vertical axis at which no modulation of the CFR was

observed during rotation about the longitudinal axis of the

vestibular rate table. In the left uvula-nodulus, a medial

sagittal strip extending through all the folia contained

Purkinje cells with CFRs that had optimal planes of

stimulation coplanar with the left posterior-right anterior

semicircular canals (LPC-RAC). Lateral to this strip was a

strip of Purkinje cells with CFRs that were characterized by

optimal planes corresponding to stimulation of the left

anterior-right posterior semicircular canals (LAC-RPC). SSs in

Purkinje cells were modulated out of phase with CFRs from

the same Purkinje cell. The depth of modulation of both CFRs

and SSs was reduced during rotation in the climbing fiber "null

plane". The depth of modulation of SSs was greatest when

recorded from Purkinje cells located at the center of

semicircular canal-related strip. We observed that 1) all folia

of the uvula-nodulus receive vestibular climbing fiber inputs;

2) these climbing fiber inputs convey information from the

vertical semicircular canals and otoliths but not the

horizontal semicircular canals; 3) CFRs evoked in a particular

sagittal zone do not influence SSs in adjacent zones; 4)

modulation of a CFRs in a particular Purkinje cell can occur

without modulation of SSs in the same Purkinje cell, although

modulation of SSs was not observed in the absence of CFR

modulation; and 5) modulation of SSs sometimes preceded that

of CFRs in the same cell, implying that interneuronal pathways

may contribute to SS modulation. Climbing fiber-driven Golgi

cells, the inhibitory axon terminals of which end on granule

cell dendrites in the classic glomerular synapse, may provide

this interneuronal mechanism.

49. Gardner, C. R.; Hussain, S.; Pringle, A.; Bagust, J.; Walker, R. J.

Comparison of responses of spontaneously active cells in the

cerebellar Purkinje layer to parallel fibre stimulation in slice

preparations and urethane-anaesthetised rats: effects of

benzodiazepine receptor ligands. Gen-Pharmacol. 1998 Jan;

30(1): 57-63; ISSN: 0306-3623.

ENGLAND. 1. GABA-mediated inhibitory responses were

induced in spontaneously active Purkinje cells by parallel

fibre stimulation in cerebellar slices or in urethane-

anaesthetised rats. Effects of agonist and inverse agonist

benzodiazepine (BDZ) receptor ligands were compared in the

preparations. 2. Purkinje cells fired simple spikes at higher

rates in slice preparations while complex spikes were seldom

(in vivo) or never observed (slice). Cells fired more regularly

in vivo resulting in the occurrence of rhythmic postinhibitory

responses in the PSTH analysis in some preparations. 3. Single

pulse stimulation of parallel fibres at just suprathreshold

intensity induced inhibition of Purkinje cell activity in both

preparations. At lower firing rates there was a marked

increase in the duration of this response, which was more

evident in vivo where more slowly firing cells were

encountered. 4. BDZ receptor ligands modified inhibitory

responses in slice preparations with only weak effects on the

firing rates of the cells. These compounds predominately

induced changes in firing rate in the anaesthetised rat with

little evidence of direct modification of GABA-mediated

synaptic transmission. 5. In a few experiments, following

injection of the partial inverse agonists beta-CCE and beta-

CCM, block of the inhibitory response was observed

independent of changes in firing rate. Bidirectional efficacy of

BDZ receptor ligand (agonists decrease firing and increase

inhibitory response, inverse agonists increase firing and

decrease inhibitory response) was demonstrated for

modulation of inhibitory responses in slices and for changes in

firing rate in vivo. The increased firing rate response in vivo

was biphasic the magnitude of the later phase being correlated

with efficacy of inverse agonists. 6. It is concluded that

cerebellar slice preparations are more appropriate for

studying direct effects of BDZ receptor ligands on GABA-

mediated synaptic inhibition than in vivo preparations.. 0; 0;

0; 0; 0; 51-79-6; 56-12-2; 94219-41-7; 99632-94-7.

50. Garwicz, M. Sagittal zonal organization of climbing fibre input to

the cerebellar anterior lobe of the ferret. Exp-Brain-Res. 1997

Dec; 117(3): 389-98; ISSN: 0014-4819.

GERMANY. The organization of climbing fibre input to the

cerebellar anterior lobe of the ferret was investigated in

barbiturate-anaesthetized animals. Climbing fibre field

potentials evoked on electrical stimulation of forelimb and

hindlimb nerves were recorded at the cerebellar surface. Based

on characteristic latencies of climbing fibre responses and

their relative localization along the longitudinal axis of the

folia, nine sagittally oriented zones could be distinguished and

were tentatively named, from medial to lateral, A, X, B, C1, Cx,

C2, C3, D1 and D2. Within the C1, C2 and C3 zones, climbing

fibre input from the ipsilateral forelimb was found caudally

and from the hindlimb rostrally, while the corresponding

topographical representation in the B and D2 zones was medial

to lateral. The X, Cx and D1 zones did not receive input from

the hindlimb, while input from the forelimb to the A zone was

weak. Overall, the sagittal zonal organization of climbing fibre

input appears to conform with the compartmentalization of

the ferret cerebellum based on the myeloarchitecture of

corticonuclear fibres, although the X and Cx zones have not

been previously identified. In terms of both general

electrophysiological characteristics of input to different

zones and intrazonal topographical representation, the

organization of climbing fibre input to the ferret cerebellum

seems to strongly resemble that in the cat. The findings thus

provide evidence of cross-species generality of cerebellar

sagittal organization.

51. Gavalas, A.; Davenne, M.; Lumsden, A.; Chambon, P.; Rijli, F. M. Role

of Hoxa-2 in axon pathfinding and rostral hindbrain patterning.

Development. 1997 Oct; 124(19): 3693-702; ISSN: 0950-1991.

ENGLAND. Segmentation plays an important role in neuronal

diversification and organisation in the developing hindbrain.

For instance, cranial nerve branchiomotor nuclei are organised

segmentally within the basal plates of successive pairs of

rhombomeres. To reach their targets, motor axons follow

highly stereotyped pathways exiting the hindbrain only via

specific exit points in the even-numbered rhombomeres. Hox

genes are good candidates for controlling this pathfinding,

since they are segmentally expressed and involved in

rhombomeric patterning. Here we report that in Hoxa-2(-/-)

embryos, the segmental identities of rhombomere (r) 2 and r3

are molecularly as well as anatomically altered. Cellular

analysis by retrograde dye labelling reveals that r2 and r3

trigeminal motor axons turn caudally and exit the hindbrain

from the r4 facial nerve exit point and not from their normal

exit point in r2. Furthermore, dorsal r2-r3 patterning is

affected, with loss of cochlear nuclei and enlargement of the

lateral part of the cerebellum. These results point to a novel

role for Hoxa-2 in the control of r2-r3 motor axon guidance,

and also suggest that its absence may lead to homeotic

changes in the alar plates of these rhombomeres.

52. Georgiadis, D.; Lindner, A. Development of cerebellar atrophy 15

years after basilar artery occlusion: hypoperfusion or

coincidence? [letter]. Eur-J-Med-Res. 1997 Dec 31; 2(12): 514;

ISSN: 0949-2321.

GERMANY.

53. Gerard, J. M.; Luisiri, A. A fatal overdose of arginine

hydrochloride. J-Toxicol-Clin-Toxicol. 1997; 35(6): 621-5;

ISSN: 0731-3810.

UNITED-STATES. CASE REPORT: Arginine hydrochloride is used

both diagnostically to test for growth hormone deficiency and

therapeutically for treatment of metabolic alkalosis. We

describe a 21-month-old girl who developed cardiopulmonary

arrest following an accidental overdose of arginine

hydrochloride. The patient developed acute metabolic acidosis

and transient, but severe, hyponatremia. Thirty-six hours after

successful resuscitation, she developed fatal central pontine

and extrapontine myelinolysis. Unlike previous reports of

arginine-toxicity, our patient showed no evidence of

hyperkalemia. This case illustrates a previously unreported

mechanism of arginine hydrochloride toxicity.. 7004-12-8;

9002-72-6.

54. Ghose, S.; Wroblewska, B.; Corsi, L.; Grayson, D. R.; De Blas, A. L.;

Vicini, S.; Neale, J. H. N-acetylaspartylglutamate stimulates

metabotropic glutamate receptor 3 to regulate expression of

the GABA(A) alpha6 subunit in cerebellar granule cells. J-

Neurochem. 1997 Dec; 69(6): 2326-35; ISSN: 0022-3042.

UNITED-STATES. We have shown that the vertebrate

neuropeptide N-acetylaspartylglutamate (NAAG) meets the

criteria for a neurotransmitter, including function as a

selective metabotropic glutamate receptor (mGluR) 3 agonist.

Short-term treatment of cerebellar granule cells with NAAG

(30 microM) results in the transient increase in content of

GABA(A) alpha6 subunit mRNA. Using quantitative PCR, this

increase was determined to be up to 170% of control values.

Similar effects are seen following treatment with trans-1-

aminocyclopentane-1,3-dicarboxylate and glutamate and are

blocked by the mGluR antagonists (2S,3S,4S)-2-methyl-2-

(carboxycyclopropyl) glycine and (2S)-alpha-ethylglutamic

acid. The effect is pertussis toxin-sensitive. The increase in

alpha6 subunit mRNA level can be simulated by activation of

other receptors negatively linked to adenylate cyclase

activity, such as adenosine A1, alpha2-adrenergic, muscarinic,

and GABA(B) receptors. Forskolin stimulation of cyclic AMP

(cAMP) levels abolished the effect of NAAG. The change in

alpha6 levels induced by 30 microM NAAG can be inhibited in a

dose-dependent manner by simultaneous application of

increasing doses of the beta-adrenergic receptor agonist

isoproterenol. The increase in alpha6 mRNA content is

followed by a fourfold increase in alpha6 protein level 6 h

posttreatment. Under voltage-clamped conditions, NAAG-

treated granule cells demonstrate an increase in the

furosemide-induced inhibition of GABA-gated currents in a

concentration-dependent manner, indicating an increase in

functional alpha6-containing GABA(A) receptors. These data

support the hypothesis that NAAG, acting through mGluR3,

regulates expression of the GABA(A) alpha6 subunit via a

cAMP-mediated pathway and that cAMP-coupled receptors for

other neurotransmitters may similarly influence GABA(A)

receptor subunit composition.. 0; 0; 0; 0; 0; 3106-85-2; 54-

31-9; 56-12-2; 60-92-4; 66428-89-5.

55. Goh, W. H.; Lo, R. A new 3C syndrome: cerebellar hypoplasia,

cavernous haemangioma and coarctation of the aorta. Dev-Med-

Child-Neurol. 1993 Jul; 35(7): 637-41; ISSN: 0012-1622.

ENGLAND. Two children were identified with facial

haemangioma, cerebellar hypoplasia and co-arctation of the

aorta; the second child presented to the neurology department

because of facial haemangioma. The importance of awareness

of the association of these three conditions is essential to

ensure proper management and survival of this group of

patients. The possible pathophysiology of these associated

conditions is discussed.

56. Goldowitz, D.; Cushing, R. C.; Laywell, E.; D'Arcangelo, G.; Sheldon,

M.; Sweet, H. O.; Davisson, M.; Steindler, D.; Curran, T.

Cerebellar disorganization characteristic of reeler in

scrambler mutant mice despite presence of reelin. J-Neurosci.

1997 Nov 15; 17(22): 8767-77; ISSN: 0270-6474.

UNITED-STATES. Analysis of the molecular basis of neuronal

migration in the mammalian CNS relies critically on the

discovery and identification of genetic mutations that affect

this process. Here, we report the detailed cerebellar phenotype

caused by a new autosomal recessive neurological mouse

mutation, scrambler (gene symbol scm). The scrambler

mutation results in ataxic mice that exhibit several

neuroanatomic defects reminiscent of reeler. The most obvious

of these lies in the cerebellum, which is small and lacks

foliation. Granule cells, although normally placed in an

internal granule cell layer, are greatly reduced in number (

approximately 20% of normal). Purkinje cells are also reduced

in number, and the majority are located ectopically in deep

cerebellar masses. There is a small population of Purkinje

cells ( approximately 5% of the total) that occupy a Purkinje

cell layer between the molecular and granule cell layers.

Despite this apparent disorganization of Purkinje cells,

zebrin-positive and zebrin-negative parasagittal zones can be

delineated. The ectopic masses of Purkinje cells are bordered

by the extracellular matrix protein tenascin and by processes

containing glial fibrillary acidic protein. Antibodies specific

for these proteins also identify a novel midline raphe

structure in both scrambler and reeler cerebellum that is not

present in wild-type mice. Thus, in many respects, the

scrambler cerebellum is identical to that of reeler. However,

the scrambler locus has been mapped to a site distinct from

that of reelin (Reln), the gene responsible for the reeler

defect. Here we find that there are normal levels of Reln mRNA

in scrambler brain and that reelin protein is secreted normally

by scrambler cerebellar cells. These findings imply that the

scrambler gene product may function in a molecular pathway

critical for neuronal migration that is tightly linked to, but

downstream of, reelin.. 0; 0; 0; 0; 0.

57. Gonzalez, J. L.; Russo, C. J.; Goldowitz, D.; Sweet, H. O.; Davisson,

M. T.; Walsh, C. A. Birthdate and cell marker analysis of

scrambler: a novel mutation affecting cortical development

with a reeler-like phenotype. J-Neurosci. 1997 Dec 1; 17(23):

9204-11; ISSN: 0270-6474.

UNITED-STATES. The reeler mutation in mice produces an

especially well characterized disorder, with systematically

abnormal migration of cerebral cortical neurons. The reeler

gene encodes a large protein, termed Reelin, that in the cortex

is synthesized and secreted exclusively in the Cajal-Retzius

neurons of the cortical marginal zone (D'Arcangelo et al.,

1995). In reeler mutant mice, loss of Reelin protein is

associated with a systematic loss of the normal, "inside-out"

sequence of neurogenesis in the cortex: neurons are formed in

the normal sequence but become localized in the cortex in a

somewhat inverted, although relatively disorganized "outside-

in" pattern. Here we show that the scrambler mutant mouse

exhibits a loss of lamination in the cortex and hippocampus

that is indistinguishable from that seen in the reeler mouse.

We use BrdU birthdating studies to show that scrambler cortex

shows a somewhat inverted "outside-in" sequence of

birthdates for cortical neurons that is similar to that

previously described in reeler cortex. Finally, we perform

staining with the CR-50 monoclonal antibody (Ogawa et al.,

1995), which recognizes the Reelin protein (D'Arcangelo et al.,

1997). We show that Reelin immunoreactivity is present in the

scrambler cortex in a normal pattern, suggesting that Reelin is

synthesized and released normally. Our data suggest that

scrambler is a mutation in the same gene pathway as the

reeler gene (Relnrl) and is most likely downstream of Relnrl..

0; 0; 0; 0; 0.

58. Green, J. T.; Woodruff, Pak DS. Concurrent eyeblink classical

conditioning and rotary pursuit performance: implications for

independent nondeclarative memory systems. Neuropsychology.

1997 Oct; 11(4): 474-87; ISSN: 0894-4105.

UNITED-STATES. The authors examined whether 2

nondeclarative tasks, simple eyeblink classical conditioning

(EBCC) and rotary pursuit (RP), would interfere with each

other when performed simultaneously. In Experiment 1,100

participants were assigned to 1 of 5 groups: paired EBCC/RP,

unpaired EBCC/RP, paired EBCC as a single task, unpaired EBCC

as a single task, and RP as a single task. Participants in the

paired EBCC/RP group showed significantly greater acquisition

of conditioned responses than did participants in the unpaired

EBCC/RP group, and the unconditioned eyeblink response was

similar in both groups. Comparisons of the paired EBCC/RP and

paired EBCC-as-a-single-task groups indicated no differences

in trials to criterion, but on some measures the single-task

group conditioned better. Controls introduced in Experiment 2

did not change this pattern. Results provide some evidence for

the lack of interference between EBCC and RP.

59. Greenberg, G.; Boyde, A. Novel method for stereo imaging in light

microscopy at high magnifications. Neuroimage. 1993 Sep;

1(2): 121-8; ISSN: 1053-8119.

UNITED-STATES. A new method for realizing direct

stereoscopic (3D) views of thick microscopic sections

employs multiple oblique illuminating beams and a single

objective lens. Excellent 3D images are obtained in the higher

magnification range, where conventional stereo microscopes

no longer function. Using conventional microscope optics,

significant increases in depth of focus and sharpness are

demonstrated.

60. Gruol, D. L.; Parsons, K. L.; DiJulio, N. Acute ethanol alters calcium

signals elicited by glutamate receptor agonists and K+

depolarization in cultured cerebellar Purkinje neurons. Brain-

Res. 1997 Oct 31; 773(1-2): 82-9; ISSN: 0006-8993.

NETHERLANDS. The effect of acute ethanol on Ca2+ signals

evoked by ionotropic (iGluR) and metabotropic (mGluR)

glutamate receptor (GluR) activation and K+ depolarization

was examined in cultured rat cerebellar Purkinje neurons to

assess the ethanol sensitivity of these Ca2+ signaling

pathways. Mature Purkinje neurons approximately 3 weeks in

vitro were studied. iGluRs were activated by (RS)-alpha-

amino-3-hydroxyl-5 methyl-4-isoxazolepropionic acid (AMPA;

1 and 5 microM) and domoate (5 microM). mGluRs were

activated by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic

acid (ACPD; 300 microM) and (R,S)-3,5-dihydroxyphenylglycine

(DHPG; 200 microM). These agents and K+ (150 mM) were

applied from micropipettes by brief (1 s) microperfusion

pulses. Ca2+ levels were monitored at 2-3 s intervals during

pre- and post-stimulus periods using microscopic digital

imaging and the Ca2+ sensitive dye fura-2. iGluR and mGluR

agonists and K+ produced abrupt increases in intracellular

Ca2+ that slowly recovered to baseline resting levels. Acute

exposure to ethanol at 33 mM (150 mg%) and 66 mM (300 mg%)

significantly reduced the amplitude of the Ca2+ signals to

iGluR agonists and K+ with little or no effect on Ca2+ signals

to mGluR agonists. In contrast, acute ethanol at 10 mM (45

mg%) had no effect on the Ca2+ signals to the iGluR agonist

AMPA but significantly enhanced the Ca2+ signals to the mGluR

agonist DHPG. These results show that ethanol modulates Ca2+

signaling linked to GluR activation in a receptor subtype

specific manner, and suggest that Ca2+ signaling pathways

linked to GluR activation and membrane depolarization may be

important mechanisms by which ethanol alters the

transduction of excitatory synaptic signals at glutamatergic

synapses and thereby affects intercellular and intracellular

communication in the CNS.. 0; 0; 0; 0; 0; 111900-32-4;

14277-97-5; 146255-66-5; 487-79-6; 52-52-8; 56-40-6;

64-17-5; 7440-09-7; 7440-70-2; 77521-29-0.

61. Gustafsson, K.; Book, M.; Dubey, J. P.; Uggla, A.

Meningoencephalitis in capercaillie (Tetrao urogallus L.)

caused by a Sarcocystis-like organism. J-Zoo-Wildl-Med. 1997

Sep; 28(3): 280-4; ISSN: 1042-7260.

UNITED-STATES. A nonsuppurative meningoencephalitis,

previously presumed to be toxoplasmosis, was found in 53

capercaillies (Tetrao urogallus L.) examined at necropsy at the

National Veterinary Institute, Uppsala, Sweden, between 1966

and 1985. Pronounced meningitis and encephalitis with

perivascular cuffs of mononuclear inflammatory cells as well

as focal gliosis were prominent histopathologic findings.

Protozoa were frequently associated with these lesions.

Ultrastructurally, the protozoa appeared to divide by

endopolygeny, and merozoites had no rhoptries. Organisms

from all 12 birds subjected to Sarcocystis cruzi

immunohistochemical staining reacted positively but did not

react to Toxoplasma gondii antiserum. The agent was,

therefore, assigned to the family Sarcocystidae and was

probably more closely related to species of the genus

Sarcocystis than to T. gondii.. 0; 0; 0.

62. Hamlyn, P. J. Neurovascular relationships in the posterior cranial

fossa, with special reference to trigeminal neuralgia. 2.

Neurovascular compression of the trigeminal nerve in

cadaveric controls and patients with trigeminal neuralgia:

quantification and influence of method. Clin-Anat. 1997; 10(6):

380-8; ISSN: 0897-3806.

UNITED-STATES. The theory of neurovascular compression has

been tested by comparing the neurovascular relationships of

the trigeminal nerve in a series of operative observations in

patients affected by trigeminal neuralgia with those of a

control series of cadavers matched for age, sex and side, in

which operative conditions were simulated during

simultaneous arterial and venous injection--filling to

physiological pressures, as described in Part 1 of this article.

A rigorous system of classification of neurovascular relations

is defined. In 46 patients with trigeminal neuralgia, 91% had a

vessel in contact with the trigeminal nerve adjacent to the

brain stem and in all but one a groove was created. Multiple

vessels were found in 17% and in two both the root entry zone

and lateral portions of the nerve were compressed. However, in

35 randomly selected fresh cadavers, not known to have

suffered neurological disease, 14% had neurovascular contact

and a further 26% had vessels "near" to the nerve. No vessel

was associated with a groove and no multiple vessels, or sites

of contact, were encountered. The difference between the

control cadavers and the operative findings in patients related

to an increase in the number of arteries. Injection-filling of

the cadaveric vessels doubled the numbers of vessels in

contact with, and near to the nerve. The technique used and

system of classification applied showed an association

between arterial contact and trigeminal neuralgia. The

technique may provide a suitable method for the testing of the

neurovascular compression theory in other conditions.

63. Hamlyn, P. J. Neurovascular relationships in the posterior cranial

fossa, with special reference to trigeminal neuralgia. 1.

Review of the literature and development of a new method of

vascular injection-filling in cadaveric controls. Clin-Anat.

1997; 10(6): 371-9; ISSN: 0897-3806.

UNITED-STATES. Vascular compression of cranial nerves

adjacent to the brain stem has been implicated in a wide

variety of disorders affecting their function. The considerable

conflicts in published results relate primarily to flaws in

study design. The design required of an adequate study is

defined and a technique is presented, in 16 fresh human

cadavers, of reliable and physiological injection-filling of

both the cerebral arterial and venous systems. It allowed for

the accurate observation of the normal neurovascular

relationships in the posterior cranial fossa during operative

simulation. Part 2 of this article concerns the use of this

design in the study of trigeminal neuralgia, a disorder thought

to relate to vascular compression of the fifth cranial nerve..

0.

64. Hampson, A. J.; Bornheim, L. M.; Scanziani, M.; Yost, C. S.; Gray, A.

T.; Hansen, B. M.; Leonoudakis, D. J.; Bickler, P. E. Dual effects

of anandamide on NMDA receptor-mediated responses and

neurotransmission. J-Neurochem. 1998 Feb; 70(2): 671-6;

ISSN: 0022-3042.

UNITED-STATES. Anandamide is an endogenous ligand of

cannabinoid receptors that induces pharmacological responses

in animals similar to those of cannabinoids such as delta9-

tetrahydrocannabinol (THC). Typical pharmacological effects

of cannabinoids include disruption of pain, memory formation,

and motor coordination, systems that all depend on NMDA

receptor mediated neurotransmission. We investigated

whether anandamide can influence NMDA receptor activity by

examining NMDA-induced calcium flux (deltaCa2+NMDA) in rat

brain slices. The presence of anandamide reduced

deltaCa2+NMDA and the inhibition was disrupted by

cannabinoid receptor antagonist, pertussis toxin treatment,

and agatoxin (a calcium channel inhibitor). Whereas these

treatments prevented anandamide inhibiting deltaCa2+NMDA,

they also revealed another, underlying mechanism by which

anandamide influences deltaCa2+NMDA. In the presence of

cannabinoid receptor antagonist, anandamide potentiated

deltaCa2+NMDA in cortical, cerebellar, and hippocampal slices.

Anandamide (but not THC) also augmented NMDA-stimulated

currents in Xenopus oocytes expressing cloned NMDA receptors,

suggesting a capacity to directly modulate NMDA receptor

activity. In a similar manner, anandamide enhanced

neurotransmission across NMDA receptor-dependent synapses

in hippocampus in a manner that was not mimicked by THC and

was unaffected by cannabinoid receptor antagonist. These data

demonstrate that anandamide can modulate NMDA receptor

activity in addition to its role as a cannabinoid receptor

ligand.. 0; 0; 0; 0; 0; 0; 0; 0; 0; 118876-58-7; 124-87-8;

1972-08-3; 6384-92-5; 70323-44-3; 7440-70-2; 94421-68-

8.

65. Hamre, K. M.; Goldowitz, D. meander tail acts intrinsic to granule

cell precursors to disrupt cerebellar development: analysis of

meander tail chimeric mice. Development. 1997 Nov; 124(21):

4201-12; ISSN: 0950-1991.

ENGLAND. The murine mutation meander tail (gene symbol:

mea) causes a near-total depletion of granule cells in the

anterior lobe of the cerebellum, as well as aberrantly located

Purkinje cells with misoriented dendrites and radial glia with

stunted processes. Whether one, two or all three of these cell

types is the primary cellular target(s) of the mutant gene is

unknown. This issue is addressed by examining cerebella from

adult chimeras in which both the genotype and phenotype of

individual cells are marked and examined. From this analysis,

three novel observations are made. First, genotypically

mea/mea Purkinje cells and glial cells exhibit normal

morphologies in the cerebella of chimeric mice indicating that

the mea gene acts extrinsically to these two cell populations.

Second, few genotypically mea/mea granule cells are present

in the anterior lobe or, unexpectedly, in the posterior lobe.

These findings indicate that the mea gene acts intrinsically to

the granule cell or its precursors to perturb their development.

Third, there are near-normal numbers of cerebellar granule

cells in the chimeric cerebellum. This result suggests that

mea/mea cells are out-competed and subsequently replaced by

an increased cohort of wild-type granule cells resulting from

an upregulation of wild-type granule cells in the chimeric

environment. We propose that the wild-type allele of the mea

gene is critical for the developmental progression of the early

granule cell neuroblast.. 9004-22-2.

66. Harrington, D. L.; Haaland, K. Y.; Knight, R. T. Cortical networks

underlying mechanisms of time perception. J-Neurosci. 1998

Feb 1; 18(3): 1085-95; ISSN: 0270-6474.

UNITED-STATES. Precise timing of sensory information from

multiple sensory streams is essential for many aspects of

human perception and action. Animal and human research

implicates the basal ganglia and cerebellar systems in

timekeeping operations, but investigations into the role of the

cerebral cortex have been limited. Individuals with focal left

(LHD) or right hemisphere (RHD) lesions and control subjects

performed two time perception tasks (duration perception,

wherein the standard tone pair interval was 300 or 600 msec)

and a frequency perception task, which controlled for deficits

in time-independent processes shared by both tasks. When

frequency perception deficits were controlled, only patients

with RHD showed time perception deficits. Time perception

competency was correlated with an independent test of

switching nonspatial attention in the RHD but not the LHD

patients, despite attention deficits in both groups. Lesion

overlays of patients with RHD and impaired timing showed

that 100% of the patients with anterior damage had lesions in

premotor and prefrontal cortex (Brodmann areas 6, 8, 9, and

46), and 100% with posterior damage had lesions in the

inferior parietal cortex. All LHD patients with normal timing

had damage in these same regions, whereas few, if any, RHD

patients with normal timing had similar lesion distributions.

These results implicate a right hemisphere prefrontal-inferior

parietal network in timing. Time-dependent attention and

working memory functions may contribute to temporal

perception deficits observed after damage to this network.

67. Hawkes, R.; Gallagher, E.; Ozol, K. Blebs in the mouse cerebellar

granular layer as a sign of structural inhomogeneity. 1.

Anterior lobe vermis. Acta-Anat-Basel. 1997; 158(3): 205-14;

ISSN: 0001-5180.

SWITZERLAND. The cerebellum is a modular structure.

However, the size of the fundamental compartments is

uncertain, with anatomical methods showing a parasagittal

band arrangement but electrophysiological mapping suggesting

a finer subdivision into microzones and patches. A new

anatomical way to demonstrate compartmentation is

described. The cerebellum is fixed by perfusion with 70%

ethanol, paraffin-embedded and sectioned. When the sections

are rehydrated the granular layer pleats into an elaborate

array of blebs. These blebs are seen in both transverse and

sagittal sections, found in all lobules of both the vermis and

the hemispheres, symmetrical about the midline, reproducible

between neighboring sections and between individuals, and

bear a constant relationship to the Purkinje cell bands as

revealed by zebrin II immunocytochemistry. The data suggest

that the granular layer of the adult mouse cerebellum is

divided into several thousand modules. These modules may

reflect the mossy fiber topography, and may be the anatomical

equivalents of the tactile receptive field patches. Such a

profound compartmentation has important implication for

theories of cerebellar structure and development.. 0; 0; 0; 64-

17-5.

68. Hayashi, R.; Tako, K.; Tokuda, T.; Yanagisawa, N. Three-Hertz

postural oscillation in patients with brain stem or cerebellar

lesions. Electromyogr-Clin-Neurophysiol. 1997 Oct; 37(7):

431-4; ISSN: 0301-150X.

BELGIUM. Postural instability was quantitatively studied in

patients with lesions in the 1) pontine tegmentum, 2) deep

cerebellar nuclei, or 3) cerebellar hemisphere. As compared to

controls, patients with each lesion demonstrated a

characteristic 3 Hertz (Hz) body oscillation. Cross-correlation

functions revealed a strong correlation between the body sway

and activities in the lower leg muscles. Based on these

findings, we conclude that the 3 Hz body oscillation may be the

result of any disturbance in the loop of long-latency reflexes

mediated by the cerebellum.

69. He, L.; Sarrafizadeh, R.; Houk, J. C. Three-dimensional

reconstruction of the rubrocerebellar premotor network of the

turtle. Neuroimage. 1995 Mar; 2(1): 21-33; ISSN: 1053-8119.

UNITED-STATES. Neuroanatomical studies have demonstrated

that the organization of the reptilian rubrocerebellar limb

premotor network is similar to that of mammals. This network

is composed of prominent recurrent connections among the red

nucleus, lateral cerebellar nucleus and lateral reticular

nucleus. In this paper the rubrocerebellar system of the turtle

was three-dimensionally reconstructed to permit detailed

examination of its anatomical organization. Each nucleus and

its major efferent pathway was imaged and reconstructed

from separate anatomical cases. Section images were used to

draw tissue boundaries, mark cell positions and locate axonal

trajectories. For each nucleus, drawings of section images

containing labeled cells were stacked in the rostrocaudal

direction using anatomical landmarks, and a graphic model of

the surface was constructed using the method of triangulation.

An ellipsoid of equal concentration was computed for each

nucleus to ascertain their three-dimensional boundaries and

location within the brainstem. To examine the entire

rubrocerebellar network, a template of the turtle brainstem

and cerebellum was constructed. The component nuclei of the

rubrocerebellar network and their axonal projections were

then spatially warped onto the template reconstruction on a

section by section basis. The final three-dimensional

reconstruction of the turtle rubrocerebellar limb premotor

network could be rotated in space, allowing proper

visualization of the anatomical details of this system.

Furthermore, we were able to mathematically section through

the reconstruction to obtain brainstem slices with differing

orientations and thickness.

70. Hessler, D.; Young, S. J.; Carragher, B. O.; Martone, M. E.; Lamont, S.;

Whittaker, M.; Milligan, R. A.; Masliah, E.; Hinshaw, J. E.;

Ellisman, M. H. Programs for visualization in three-

dimensional microscopy. Neuroimage. 1992 Aug; 1(1): 55-67;

ISSN: 1053-8119.

UNITED-STATES. Three-dimensional data representing

biological structures can be derived using several methods,

including serial section reconstruction, optical sectioning, and

tomography. The investigation, comprehension, and

communication of structural relationships to others is greatly

facilitated by computer-based visualization procedures. We

describe SYNU, a suite of programs developed for interactive

investigation of three-dimensional structure and for the

production of high-quality three-dimensional images and

animations. We illustrate the capabilities of SYNU in

applications to biological data obtained by confocal light

microscopy, serial section, and high-resolution electron

microscopy from investigations at the cellular, subcellular,

and molecular levels.

71. Hockberger, P. E.; Yousif, L.; Nam, S. C. Identification of acutely

isolated cells from developing rat cerebellum. Neuroimage.

1994 Nov; 1(4): 276-87; ISSN: 1053-8119.

UNITED-STATES. Immunocytochemical staining was used to

identify nerve and glial cells from postnatal rat cerebelli in

situ and following tissue dissociation. Purkinje cells were

identified using antibodies for the calcium-binding proteins

calbindin and PEP19. Purkinje cells isolated during the second

postnatal week were 15-20 microns in diameter and relatively

abundant and displayed thin perisomatic processes. These

features were used to identify Purkinje cells with scanning

electron microscopy, which revealed extensive membrane

infoldings. Golgi and nuclear cells were identified using

antibodies against rat-303 antigen. Pale, nuclear, and Purkinje

cells were identified using antibodies for rat-302 antigen.

Although staining for rat-302 and rat-303 was weak during

the second postnatal week, we were able to identify Golgi and

pale cells even after tissue dissociation. Isolated Golgi cells

were 8-10 microns in diameter and fewer in number than

Purkinje cells and did not counterstain with calbindin

antibodies. Isolated pale cells were 8-10 microns in diameter,

rare, and resistant to calbindin antibodies. Isolated neurons

from cerebellar nuclei were not located with either 302 or

303 staining, suggesting that they remained in the tissue.

Golgi-Bergmann cells and astrocytes were identified using

antibodies for glial fibrillary acidic protein. Isolated glial

cells were 12-15 microns in diameter, more numerous than

Purkinje cells, and unstained with calbindin antibodies. With

phase-contrast optics, glial cells appeared flatter than

neuronal cell types and had acentric nuclei. These results

demonstrate that specific cell types in developing rat

cerebellum can be identified after acute isolation, which

should facilitate analysis of their endogenous properties.

72. Hollrigel, G. S.; Morris, R. J.; Soltesz, I. Enhanced bursts of IPSCs

in dentate granule cells in mice with regionally inhibited long-

term potentiation. Proc-R-Soc-Lond-B-Biol-Sci. 1998 Jan 7;

265(1390): 63-9; ISSN: 0962-8452.

ENGLAND. Until recently, most studies on the synaptic-

cellular basis of learning and memory concentrated on the

activity-dependent changes occurring in principal cells such

as hippocampal pyramidal cells and dentate granule cells.

However, the ability of the inhibitory interneurons to regulate

synaptic plasticity remains less understood. This study tested

the hypothesis that the gamma-aminobutyric-acid (GABA)-

mediated inhibitory neurotransmission is enhanced in mice

that show no detectable long-term potentiation in the dentate

gyrus in the absence of the GABAA receptor antagonist

bicuculline. Patch clamp recordings were made from dentate

granule cells in brain slices from wild-type and Thy-1

knockout (KO) mice. The frequency, amplitude and kinetics of

miniature inhibitory postsynaptic currents (mIPSCs, generated

by the action potential-independent release of GABA) was not

different between animals. However, bursts of spontaneous

IPSCs (sIPSCs, generated by both action potential-independent

and -dependent GABA release) in KO mice were associated

with larger synaptic charge transfers and increased durations.

When pairs of IPSCs were evoked at varying intervals, the

amplitude of the second response with respect to the first

was significantly larger in KO animals. These results further

support the concept that enhancement of interneuronal

functions in cortical structures can have profound effects on

the activity-dependent synaptic plasticity observed in

principal cells.. 0; 56-12-2.

73. Hu, W. H.; Wang, J. J.; Zhang, M. Y.; Yu, Q. X. [Effects of NA and 5-HT

on the spontaneous and evoked activities of Purkinje cells in

cerebellar slice]. Sheng-Li-Hsueh-Pao. 1996 Dec; 48(6): 581-6;

ISSN: 0371-0874.

CHINA. Effects of NA and 5-HT perfusion on the spontaneous

activity and evoked responses of the Purkinje cells (PCs) to

stimulation of white matter were studied in the rat cerebellar

slices. The results were as follows: (1) Perfusion with NA

could elicit inhibitory, excitatory or biphasic responses of the

spontaneously discharging PCs, with inhibitory response in

dominance (79.8%). 5-HT perfusion could also exert either

excitatory or inhibitory effect on PC spontaneous activity. (2)

When NA and 5-HT were perfused successively, NA tended to

inhibit while 5-HT tended to excite in 53.8% of the tested

cells. (3) Most of the complex spike (CS) and simple spike (SS)

responses evoked by white matter stimulation could be

potentiated by NA (68.2%, 57.1%) or depressed by 5-HT (60.0%,

68.2%). (4) On the same cell under successively perfusion with

NA and 5-HT, the evoked CS and SS responses of most cells

(60.0%, 52.9%) showed a tendency to be facilitated by NA and

suppressed by 5-HT. These results suggest that aminergic

afferent fibers, by releasing NA and 5-HT, may affect PC's

excitability and responsiveness to synaptic inputs from mossy

and climbing fibers, thus playing an important role in the

cerebellar function.. 50-67-9; 51-41-2.

74. Ito, K.; Ishikawa, Y.; Skinner, R. D.; Mrak, R. E.; Morrison Bogorad,

M.; Mukawa, J.; Griffin, W. S. Lesioning of the inferior olive

using a ventral surgical approach. Characterization of

temporal and spatial astrocytic responses at the lesion site

and in cerebellum. Mol-Chem-Neuropathol. 1997 Aug; 31(3):

245-64; ISSN: 1044-7393.

UNITED-STATES. Activated astrocytes, intrinsic components

of both local and remote (axonal target regions) central

nervous system injury responses, are now recognized as active

metabolic and regulatory mediators in many neurological

disorders. To further define these responses, we devised a new

ventral surgical approach to unilaterally lesion the inferior

olivary nuclear complex, which has a single predominant

remote target, the cerebellum. Activated astrocyte number,

volume, and density, as well as the total volume of brainstem

involved in the astrocytic response, all peaked at postlesion

day (pld) 4, returning toward, but not to, unoperated control

values at pld 24 (p < 0.05). In contrast, the peak astrocyte

response in the cerebellum was delayed, being greatest at pld

6 (p < 0.05 compared to control or pld 2). These responses were

associated with increases in overexpression of S100 beta, an

astrocyte-derived neurite growth factor, and with an increase

in cerebellar steady-state levels of a neuronal injury response

protein, the beta-amyloid precursor protein (beta-APP). This

is similar to correlated increases in these two proteins that

are found in epilepsy and Alzheimer disease. Our studies

defining remote astrocytic and neuronal responses may be

important for understanding glial-neuronal mechanisms

underlying the spread of neuropathological changes in

conditions such as Alzheimer disease.. 0; 0; 0.

75. Itoh, M.; Watanabe, Y.; Watanabe, M.; Tanaka, K.; Wada, K.;

Takashima, S. Expression of a glutamate transporter subtype,

EAAT4, in the developing human cerebellum. Brain-Res. 1997

Sep 5; 767(2): 265-71; ISSN: 0006-8993.

NETHERLANDS. A glutamate transporter subtype, EAAT4, is

closely related to removal of glutamate from the synaptic

cleft. Immunohistochemistry for EAAT4 demonstrated the

specific distribution and localization of its expression in the

developing human cerebellum. Purkinje cells showed faint

EAAT4 immunostaining at 17 gestational weeks (GW), which

became increasingly intense from 23 GW to the infantile

period. In the late fetal to early infantile periods, Purkinje

cells showed marked immunoreactivity. After the late

infantile period, EAAT4 immunoreactivity was the same in

extent as in the adult pattern. Its intracellular localization

also changed with development. EAAT4 immunoreactivity was

demonstrated in the short processes of Purkinje cells in the

early embryonic period, in the cell bodies and dendrites in the

late fetal to early infantile periods, and then in the spines

after the late infantile period. In the adult cerebellum,

immunoreactivity was detected strongly in the spines of

Purkinje cells and weakly in the cell bodies. No

immunoreactivity was found in the axons or axon terminals of

the cells. Thus, the glutamate transporter exhibits

developmental changes in its distribution in the cerebellum

and its localization in Purkinje cells. EAAT4 immunoreactivity

may be related to the dendritic arborization of cells in the

molecular layer.. 0; 0; 0.

76. Jacobsen, L. K.; Giedd, J. N.; Berquin, P. C.; Krain, A. L.; Hamburger,

S. D.; Kumra, S.; Rapoport, J. L. Quantitative morphology of the

cerebellum and fourth ventricle in childhood-onset

schizophrenia. Am-J-Psychiatry. 1997 Dec; 154(12): 1663-9;

ISSN: 0002-953X.

UNITED-STATES. OBJECTIVE: Studies have suggested that the

maldeveloped neural circuitry producing schizophrenic

symptoms may include the cerebellum. The authors found

further support for this hypothesis by examining cerebellar

morphology in severely ill children and adolescents with

childhood-onset schizophrenia. METHOD: Anatomic brain scans

were acquired with a 1.5-T magnetic resonance imaging

scanner for 24 patients (mean age = 14.1 years, SD = 2.2) with

onset of schizophrenia by age 12 (mean age at onset = 10.0

years, SD = 1.9) and 52 healthy children. Volumes of the

vermis, inferior posterior lobe, fourth ventricle, and total

cerebellum and the midsagittal area of the vermis were

measured manually. RESULTS: After adjustment for total

cerebral volume, the volume of the vermis and the midsagittal

area and volume of the inferior posterior lobe remained

significantly smaller in the schizophrenic patients. There was

no group difference in total cerebellar or fourth ventricle

volume. CONCLUSIONS: These findings are consistent with

observations of small vermal size in adult schizophrenia and

provide further support for abnormal cerebellar function in

childhood- and adult-onset schizophrenia.

77. Jan, J. E.; Kearney, S.; Groenveld, M.; Sargent, M. A.; Poskitt, K. J.

Speech, cognition, and imaging studies in congenital ocular

motor apraxia. Dev-Med-Child-Neurol. 1998 Feb; 40(2): 95-9;

ISSN: 0012-1622.

ENGLAND. Detailed neurological, speech and language,

psychological, and neuroimaging studies were carried out in

eight children with the diagnosis of congenital ocular motor

apraxia. The neurological examination showed clinical

evidence of cerebellar vermis abnormality (hypotonia and

truncal ataxia) in all cases. Neuroimaging studies suggested

that the site of neuropathological disturbance of congenital

ocular motor apraxia was the inferior vermis. Half of the

subjects had associated speech apraxia. The most likely

location of brain disturbance, which was responsible for the

speech apraxia, was also an as yet undefined area of the

vermis. Psychological testing consistently revealed visual-

spatial difficulties. These may have been secondary to

cerebellar pathology or to developmentally inappropriate

sensory input caused by the abnormal saccades. Children with

speech apraxia appear to be slightly more affected

neurologically than those with normal speech.

78. Jonas, S.; Sugimori, M.; Llinas, R. Is low molecular weight heparin

a neuroprotectant? Ann-N-Y-Acad-Sci. 1997 Oct 15; 825: 389-

93; ISSN: 0077-8923.

UNITED-STATES. This communication reports the results of

investigations on the effect of low molecular weight heparin

(LMWH) on intraneuronal calcium release, and considers its

possible relevance to the treatment of ischemic stroke. It

previously was shown that intraneuronal injection of

conventional heparin (MW 12,000) in vitro prevents glutamate-

induced calcium release from intracellular stores through its

blocking action on IP3 (inositol-1,4,5-triphosphate) receptors,

and thus interferes with events occurring in the ischemic

cascade. In the experiments reported herein, a LMWH of MW

4500 was shown to have these same effects when injected

into a Purkinje cell in an in vitro cerebellar slice preparation,

and also when administered externally (bath application). By

contrast, conventional heparin works only when injected into

the cell; bath application has no effect. The results are

interpreted to mean that the larger conventional heparin

molecule cannot pass through the cell membrane, while the

smaller LMWH molecule does indeed enter the cell. In a clinical

trial, LMWH begun within 48 hours of ischemic stroke onset in

humans improved outcome at 6 months; conventional heparin

given in a similar trial was without benefit. That one

anticoagulant was beneficial while another failed suggests the

possibility that the difference was independent of effect on

the clotting system. The experimental data herein reported

support the view that LMWH may benefit stroke victims by an

action directly cytoprotective against the consequences of

neuronal ischemia.. 0; 0; 0; 7440-70-2.

79. Jueptner, M.; Ottinger, S.; Fellows, S. J.; Adamschewski, J.;

Flerich, L.; Muller, S. P.; Diener, H. C.; Thilmann, A. F.; Weiller,

C. The relevance of sensory input for the cerebellar control of

movements. Neuroimage. 1997 Jan; 5(1): 41-8; ISSN: 1053-

8119.

UNITED-STATES. The performance of a motor task not only

requires subjects to plan, prepare, and initiate but also to

monitor how a movement is performed. We used positron

emission tomography to examine to what extent the human

cerebellum is involved in controlling motor output or sensory

input from movements in normal subjects. In the first study,

we compared the active performance of a motor task (flexion

and extension of the right elbow) to the passive execution of

the same movements. Passive movements were driven by a

motor with the arm fixed in a guide hinge. Active movements

(compared to rest) elicited increases of rCBF mainly in the

ipsilateral neocerebellar hemisphere and vermis of the

posterior lobe. During passive movements, almost identical

parts of the cerebellar hemispheres and vermis were activated

(compared to the rest condition). The direct comparison of

active and passive movement conditions revealed a small

activation of the neocerebellar hemisphere of the posterior

lobe and cerebellar nuclei ipsilateral to the movement.

Approximately 90% of cerebellar neuronal activity was related

to sensory input. In the second study, we compared the

execution of a free selection joystick movement task to a

condition in which subjects simply imagined the movements.

The execution of movements (compared to rest) was

associated with increases of rCBF in the ipsilateral

neocerebellar hemisphere and vermis of the posterior lobe.

During movement imagination, a small part of the ipsilateral

cerebellar hemisphere and vermis of the posterior lobe was

activated (compared to rest). The increase of rCBF during

movement imagination accounted for only 20% of the signal

seen during movement execution. Our results indicate that the

neocerebellum may be much more concerned with sensory

information processing than has been considered previously.

80. Kawaja, M. D.; Walsh, G. S.; Petruccelli, K.; Coome, G. E. Sensory

nociceptive axons invade the cerebellum of transgenic mice

overexpressing nerve growth factor. Brain-Res. 1997 Nov 7;

774(1-2): 77-86; ISSN: 0006-8993.

NETHERLANDS. Transgenic mice possessing elevated levels of

mRNA expression and synthesis for the neurotrophin nerve

growth factor among astrocytes display a robust ingrowth of

new sympathetic fibers to the cerebellum. In this

investigation, we report that the cerebellum of these mice

also possesses a dense plexus of aberrant axons of sensory

origin. Axons stained immunohistochemically for calcitonin

gene-related peptide were seen in the transgenic cerebellum

as early as one week after birth. The density of these axons

dramatically increased with age. Immunopositive axons were

confined predominantly to the deep white matter of the

cerebellum in the adult transgenic mice, with a smaller

number of axons seen coursing along blood vessels in the gray

matter. Axons stained immunohistochemically for the

neurotrophin receptor, p75NTR, displayed a similar pattern of

distribution and density as those immunostained for calcitonin

gene-related peptide. Wild-type post-natal and adult animals

lacked such calcitonin gene-related peptide- and p75NTR-

immunoreactive axons in the cerebellum. Retrograde labelling

revealed that these axons within the transgenic cerebellum

originated from neurons in the sensory trigeminal and dorsal

root ganglia (upper cervical levels). This investigation

demonstrates that overexpression of nerve growth factor is

capable of inducing the directional growth of collateral axons

of sensory neurons into the undamaged mammalian central

nervous system.. 0.

81. Kenyon, G. T. A model of long-term memory storage in the

cerebellar cortex: a possible role for plasticity at parallel

fiber synapses onto stellate/basket interneurons. Proc-Natl-

Acad-Sci-U-S-A. 1997 Dec 9; 94(25): 14200-5; ISSN: 0027-

8424.

UNITED-STATES. By evoking changes in climbing fiber

activity, movement errors are thought to modify synapses

from parallel fibers onto Purkinje cells (pf*Pkj) so as to

improve subsequent motor performance. Theoretical arguments

suggest there is an intrinsic tradeoff, however, between motor

adaptation and long-term storage. Assuming a baseline rate of

motor errors is always present, then repeated performance of

any learned movement will generate a series of climbing

fiber-mediated corrections. By reshuffling the synaptic

weights responsible for any given movement, such corrections

will degrade the memories for other learned movements stored

in overlapping sets of synapses. The present paper shows that

long-term storage can be accomplished by a second site of

plasticity at synapses from parallel fibers onto

stellate/basket interneurons (pf*St/Bk). Plasticity at

pf*St/Bk synapses can be insulated from ongoing fluctuations

in climbing fiber activity by assuming that changes in

pf*St/Bk synapses occur only after changes in pf*Pkj

synapses have built up to a threshold level. Although climbing

fiber-dependent plasticity at pf*Pkj synapses allows for the

exploration of novel motor strategies in response to changing

environmental conditions, plasticity at pf*St/Bk synapses

transfers successful strategies to stable long-term storage.

To quantify this hypothesis, both sites of plasticity are

incorporated into a dynamical model of the cerebellar cortex

and its interactions with the inferior olive. When used to

simulate idealized motor conditioning trials, the model

predicts that plasticity develops first at pf*Pkj synapses, but

with additional training is transferred to pf*St/Bk synapses

for long-term storage.

82. Khodakhah, K.; Armstrong, C. M. Induction of long-term depression

and rebound potentiation by inositol trisphosphate in

cerebellar Purkinje neurons. Proc-Natl-Acad-Sci-U-S-A. 1997

Dec 9; 94(25): 14009-14; ISSN: 0027-8424.

UNITED-STATES. Cerebellar Purkinje neurons receive two

major excitatory inputs, the climbing fibers (CFs) and parallel

fibers (PFs). Simultaneous, repeated activation of CFs and PFs

results in the long-term depression (LTD) of the amplitude of

PF-evoked synaptic currents. To induce LTD, activation of CFs

may be substituted with depolarization of the Purkinje neuron

to turn on voltage-activated calcium channels and increase the

intracellular calcium concentration. The role of PFs in the

induction of LTD, however, is less clear. PFs activate

glutamate metabotropic receptors that increase

phosphoinositide turnover and elevate cytosolic inositol 1,4,5-

trisphosphate (InsP3). It has been proposed that calcium

release from intracellular stores via InsP3 receptors may be

important in the induction of LTD. We studied the role of InsP3

in the induction of LTD by photolytic release of InsP3 from its

biologically inactive "caged" precursor in voltage-clamped

Purkinje neurons in acutely prepared cerebellar slices. We find

that InsP3-evoked calcium release is as effective in LTD

induction as activation of PFs. InsP3-induced LTD was

prevented by calcium chelator 1,2-bis(2-amino

phenoxy)ethane-N,N,N', N'-tetraacetic acid. LTD produced either

by repeated activation of PFs combined with depolarization

(PF+DeltaV), or by InsP3 combined with depolarization

(InsP3+DeltaV) saturated at approximately 50%. Maximal LTD

induced by PF+DeltaV could not be further increased by

InsP3+DeltaV and vice versa, which suggests that both

protocols for induction of LTD share a common path. In

addition to inducing LTD, photo-release of InsP3+DeltaV

resulted in the rebound potentiation of inhibitory synaptic

currents. In the presence of heparin, an InsP3 receptor

antagonist, repeated activation of PF+DeltaV failed to induce

LTD, suggesting that InsP3 receptors play an important role in

LTD induction under physiological conditions.. 7440-70-2;

85166-31-0.

83. Kim, J. J.; Krupa, D. J.; Thompson, R. F. Inhibitory cerebello-olivary

projections and blocking effect in classical conditioning.

Science. 1998 Jan 23; 279(5350): 570-3; ISSN: 0036-8075.

UNITED-STATES. The behavioral phenomenon of blocking

indicates that the informational relationship between the

conditioned stimulus and the unconditioned stimulus is

essential in classical conditioning. The eyeblink conditioning

paradigm is used to describe a neural mechanism that

mediates blocking. Disrupting inhibition of the inferior olive, a

structure that conveys unconditioned stimulus information

(airpuff) to the cerebellum prevented blocking in rabbits.

Recordings of cerebellar neuronal activity show that the

inferior olive input to the cerebellum becomes suppressed as

learning occurs. These results suggest that the inferior olive

becomes functionally inhibited by the cerebellum during

conditioning, and that this negative feedback process might be

the neural mechanism mediating blocking.. 124-87-8; 56-12-

2.

84. Kim, J. S.; Lee, J. H.; Choi, C. G. Patterns of lateral medullary

infarction: vascular lesion-magnetic resonance imaging

correlation of 34 cases. Stroke. 1998 Mar; 29(3): 645-52; ISSN:

0039-2499.

UNITED-STATES. BACKGROUND AND PURPOSE: Correlation of

MRI findings with various vascular pathologies has rarely been

attempted in patients with lateral medullary infarction (LMI).

The aim of the present study was to correlate the diverse MRI

lesions with the vascular lesions seen on conventional

cerebral angiography in LMI. METHODS: The subjects included

34 patients with LMI who underwent both MRI and conventional

angiography. We analyzed the risk factors, clinical features,

MRI findings, and angiography results. The size of the

infarction was also measured. We attempted to correlate the

MRI findings with the vascular lesions shown in the

angiograms. RESULTS: Presumed causes for infarction were

atherothrombosis in 19 patients, arterial dissection in 8,

cardiogenic embolism in 3, moyamoya disease in 1, small-

vessel disease in 1, and embolism of unknown source in 2.

Isolated posterior inferior cerebellar artery (PICA) disease (n

= 8) was usually associated with atherothrombosis and

correlated with thin, round, or diagonal band-shaped lesions in

the lateral-superficial area of the caudal medulla and/or

dorsolateral portion of the rostral-middle medulla. Short-

segment distal vertebral artery (VA) disease (n = 9) was

usually due to atherothrombosis and correlated with small

lateral caudal and/or medium-sized, diagonal band-shaped

rostral-middle medullary lesions. There were 13 patients with

long-segment VA disease sparing (n = 8) or involving (n = 5)

the proximal part of the VA with concomitant occlusion of the

PICA in 7 patients. This vascular lesion produced either large

MRI lesions extending ventrally (n = 5; 4 were associated with

VA dissection) or small lesions mimicking those produced by

isolated PICA disease (n = 8; 6 were associated with

atherothrombosis and 1 patient had moyamoya disease). These

large MRI lesions characteristically produced bilateral or

contralateral trigeminal sensory involvement. Normal

angiogram (n = 4; 3 patients were presumed to have cardiac

embolism, one lesion was associated with small-vessel

infarction) was associated with small, round lesions that

produced minor and fragmentary symptoms. Among these

subgroups, the size of the infarct in the patients with long-

segment VA disease due to dissection was significantly larger

than that of the patients with other vascular lesions.

CONCLUSIONS: Our data suggest that the heterogeneous MRI

lesions (and consequent clinical syndromes) of LMI are

correlated with diverse angiographic findings, which in turn

are due to different pathogenic mechanisms: etiology, location

and size of the involved vessels, speed of the lesion

development, and status of collateral channels. Generally,

infarcts related to multiple vessel involvement, dissection,

and poor collateral circulation are larger than those

associated with single-vessel disease, long-standing

atherothrombosis/cardiac embolism, and good

collateralization.

85. Kim, M. S.; Jin, B. K.; Chun, S. W.; Lee, M. Y.; Lee, S. H.; Kim, J. H.;

Park, B. R. Effect of MK801 on cFos-like protein expression in

the medial vestibular nucleus at early stage of vestibular

compensation in uvulonodullectomized rats. Neurosci-Lett.

1997 Aug 15; 231(3): 147-50; ISSN: 0304-3940.

IRELAND. The purpose of this study was to evaluate the effect

of uvulonodullectomy (UNL) on the expression of cFos-like

protein (FLP) in the medial vestibular nucleus (MVe) during

vestibular compensation and effect of MK801, an N-methyl-D-

aspartate (NMDA) antagonist, on FLP expression in the brain

stem nuclei at 6 h after unilateral labyrinthectomy (ULX) with

UNL in Sprague-Dawley rats. Immunohistochemical staining

was performed to visualize FLP in the brain stem nuclei and

FLP-positive cells were counted by image analyzer. Lesion-

induced asymmetric expression of FLP in the bilateral MVe

was observed and maintained up to for 72 h in the ULX group,

and 120 h in the UNL + ULX group. Moreover, spatial pattern of

FLP expression in the bilateral MVe exhibited the marked

difference between the ULX and UNL + ULX groups. MK801

treatment 6 h after ULX showed significant increase in the

number of FLP in contralateral MVe (cMVe) of the ULX group,

but decrease in cMVe of the UNL + ULX group. These results

suggest that the lesion of vestibulocerebellum delays the

temporal recovery of FLP expression in MVe and the

vestibulocerebellar NMDA receptors relate to FLP expression

in MVe.. 0; 0; 0; 77086-22-7.

86. King, V. M.; Armstrong, D. M.; Apps, R.; Trott, J. R. Numerical

aspects of pontine, lateral reticular, and inferior olivary

projections to two paravermal cortical zones of the cat

cerebellum. J-Comp-Neurol. 1998 Jan 26; 390(4): 537-51;

ISSN: 0021-9967.

UNITED-STATES. Two different olivo-cortico-nuclear zones in

the cat cerebellum have been compared quantitatively as

regards the numbers of cells projecting to them from within

several sources of mossy fibres (MFs), namely the basal

pontine nuclei (BPN), nucleus reticularis tegmenti pontis

(NRTP), and the ipsilateral lateral reticular nucleus (LRN). The

zones chosen were the C3 zone in lobule V of the anterior lobe

and the C1 zone in pars copularis of the paramedian lobule

(PMLpc), localised by recording climbing fibre-mediated

potentials evoked on their surface as a result of volleys set up

in their spino-olivocerebellar paths. The zones were injected

with fluorescent-labelled latex microspheres and cell bodies,

retrogradely labelled in the MF source nuclei and in the

contralateral inferior olive, were counted and mapped.

Evidence was obtained that tracer efficiency was very high in

both the MF projections and the olivo-cerebellar projection

and that each olivocerebellar axon may provide only one

climbing fibre to the upper part of a lobule V folium but an

average of nearly two to the same part of a PML folium. When

the numbers of labelled cells in each MF source nucleus were

expressed as a percentage of the total number of labelled

pontine cells, the biggest source for lobule V was the

contralateral BPN, followed by LRN, contralateral NRTP,

ipsilateral BPN, and ipsilateral NRTP. For PMLpc, the order was

similar except that ipsilateral BPNs exceeded contralateral

NRTPs, but the dominance of contralateral BPN as a source was

much greater. Cell totals were converted into projection

densities (i.e., numbers of cells labelled per square millimetre

of cortical sheet involved in the injection site); densities for

PMLpc were found to be almost three times greater than those

for lobule V for contralateral BPN but the two densities were

not significantly different for ipsilateral BPN. The three other

MF sources projected at higher densities to lobule V than to

PML. These findings indicate that two cortical zones, both of

which receive climbing fibres from the rostral part of the

dorsal accessory olive and project to nucleus interpositus

anterior, nevertheless differ markedly in regard to both the

relative and the absolute sizes of the projections they receive

from several of their most important sources of MFs.

87. Kishimoto, Y.; Kawahara, S.; Kirino, Y.; Kadotani, H.; Nakamura, Y.;

Ikeda, M.; Yoshioka, T. Conditioned eyeblink response is

impaired in mutant mice lacking NMDA receptor subunit NR2A.

Neuroreport. 1997 Dec 1; 8(17): 3717-21; ISSN: 0959-4965.

ENGLAND. NMDA receptor channels, heteromeric assemblies of

subunits with diverse subtypes, play critical roles in various

kinds of synaptic plasticity underlying learning and memory.

To elucidate the roles of subunits NR2A and NR2C in motor

learning, we investigated acquisition of the classically

conditioned eyeblink response in a delayed-conditioning

paradigm by gene knockout mice. Mutant mice lacking NR2C

exhibited no significant defect; however, early acquisition of

the task was impaired in mutant mice lacking NR2A or both

NR2A and NR2C. Based on the distribution of these subunits in

brain, these results indicate that acquisition of the

conditioned response does not depend on NMDA receptors in the

cerebellar cortex, but that its early acquisition involves the

hippocampus and/or cerebellar deep nuclei.. 0; 7440-70-2.

88. Kleim, J. A.; Vij, K.; Ballard, D. H.; Greenough, W. T. Learning-

dependent synaptic modifications in the cerebellar cortex of

the adult rat persist for at least four weeks. J-Neurosci. 1997

Jan 15; 17(2): 717-21; ISSN: 0270-6474.

UNITED-STATES. Several experiments have demonstrated

increased synapse number within the cerebellar cortex in

association with motor skill learning but not with motor

activity alone. The persistence of these synaptic changes in

the absence of continued training was examined in the present

experiment. Adult female rats were randomly allocated to

either an acrobatic condition (AC) or a motor activity

condition (MC). The AC animals were trained to traverse a

complex series of obstacles, and each AC animal was pair-

matched with an MC animal that traversed an obstacle-free

runway. These animals were further assigned to one of three

training conditions. Animals in the EARLY condition were

trained for 10 consecutive days before being killed, animals in

the DELAY, condition received the same 10 d of training

followed by a 28 d period without training, and animals in the

CONTINUOUS condition were trained for the entire 38 d.

Unbiased stereological techniques were used to obtain

estimates of the number of synapses per Purkinje cell within

the cerebellar paramedian lobule. Results showed the AC

animals to have significantly more synapses per Purkinje cell

than the MC animals in all three training conditions. There

were no differences in the number of synapses per Purkinje

cell among the EARLY, DELAY, and CONTINUOUS conditions.

These data demonstrate that both the motor skills and the

increases in synapse number presumed to support them persist

in the absence of continued training.

89. Klintsova, A. Y.; Matthews, J. T.; Goodlett, C. R.; Napper, R. M.;

Greenough, W. T. Therapeutic motor training increases parallel

fiber synapse number per Purkinje neuron in cerebellar cortex

of rats given postnatal binge alcohol exposure: preliminary

report. Alcohol-Clin-Exp-Res. 1997 Oct; 21(7): 1257-63; ISSN:

0145-6008.

UNITED-STATES. Because therapeutic approaches to fetal

alcohol effects in humans have been rare, this study explored

the rehabilitative effect of complex motor training on an

animal model of binge drinking in the third trimester of human

pregnancy. Neonatal alcohol exposure induces significant and

permanent reductions in Purkinje and granule cell number

accompanied by impaired motor behavior in rats. The purpose

of this study was to determine: (1) whether the motor skill

impairment caused by exposure to alcohol in the early

postnatal period could be ameliorated by the learning of a set

of complex motor tasks that had been demonstrated to cause

synaptogenesis in the cerebellar cortex; and (2) the extent to

which cerebellar neurons in alcohol-exposed (AE) rats exhibit

synaptic plasticity. The AE group was given 4.5 g/kg/day of

ethanol from postnatal days 4 to 9 via an artificial rearing

procedure producing a mean peak blood alcohol level of 257

mg/dl. Control groups consisted of a gastrostomy control (GC)

group, that received an isocaloric mixture of maltose/dextrin

instead of ethanol, and a suckle control (SC) group, that was

reared normally by dams. At approximately 6 months of age,

animals from the three groups were assigned either to a

rehabilitation condition (RC; that received 10 days of training

on the motor tasks) or to an inactive condition (IC; where rats

stayed in isolation in their cages). Although SC rats were

significantly faster to complete the course in the first 5 days

of training, there were no differences in ability to perform

among animals from all three groups-SC, GC, and AE--at the

end of the training period. Unbiased stereological techniques

were used to obtain estimates of the number of parallel fiber

synapses/Purkinje cell within the cerebellar paramedian

lobule. Results showed that the RC rats from the SC and AE

groups had significantly more synapses/Purkinje cell than

corresponding IC animals. These data demonstrate that

rehabilitative intervention (complex motor training) can

improve motor performance impaired by postnatal alcohol

exposure and that surviving Purkinje neurons retain the

capacity for synaptic plasticity.. 0; 64-17-5.

90. Kluge, A.; Kettner, B.; Zschenderlein, R.; Sandrock, D.; Munz, D. L.;

Hesse, S.; Meierkord, H. Changes in perfusion pattern using

ECD-SPECT indicate frontal lobe and cerebellar involvement in

exercise-induced paroxysmal dystonia. Mov-Disord. 1998 Jan;

13(1): 125-34; ISSN: 0885-3185.

UNITED-STATES. The clinical features of exercise-induced

paroxysmal dystonia (EPD) are delineated in a pedigree

including two affected members (both male) showing an

autosomal-dominant inheritance trait. Gait analysis using

kinematic electromyography during the motor attacks revealed

coactivation of antagonistic calf muscles characteristic of

dystonia. In the interval, impaired muscular alternation was

observed. To characterize further the pathophysiological basis

of the condition, ictal and interictal cerebral perfusion SPECT

studies using technetium 99m-ethyl cysteinate dimer (ECD)

were performed to establish whether cortical hyperactivity

indicative of epilepsy is present during the motor attacks and

to identify regional changes in the ictal perfusion pattern that

could indicate an anatomic structure relevant to the disease.

During the motor attacks, decreased ictal perfusion of the

frontal cortex was found in both patients. In contrast,

increased cerebellar perfusion was observed. The perfusion of

the basal ganglia also decreased. No cortical hyperperfusion

indicative of an epileptic nature was seen. Cerebellar

hyperactivity in connection with prominent frontal

hypoactivity has also been described in both the idiopathic and

the symptomatic forms of dystonia. Our findings therefore

suggest that EPD represents a paroxysmal movement disorder

rather than epilepsy. It is concluded that changes in frontal

and in cerebellar function are relevant to the pathophysiology

of EPD.

91. Koide, R.; Onodera, O.; Ikeuchi, T.; Kondo, R.; Tanaka, H.; Tokiguchi,

S.; Tomoda, A.; Miike, T.; Isa, F.; Beppu, H.; Shimizu, N.;

Watanabe, Y.; Horikawa, Y.; Shimohata, T.; Hirota, K.; Ishikawa,

A.; Tsuji, S. Atrophy of the cerebellum and brainstem in

dentatorubral pallidoluysian atrophy. Influence of CAG repeat

size on MRI findings. Neurology. 1997 Dec; 49(6): 1605-12;

ISSN: 0028-3878.

UNITED-STATES. To elucidate how the size of the expanded

CAG repeat of the gene for dentatorubral pallidoluysian

atrophy (DRPLA) and other factors affect the atrophy of the

brainstem and cerebellum, and the appearance of high-

intensity signals on T2-weighted MRI of the cerebral white

matter of patients with DRPLA, we quantitatively analyzed the

MRI findings of 26 patients with DRPLA, the diagnosis of

which was confirmed by molecular analysis of the DRPLA gene.

When we classified the patients into two groups based on the

size of the expanded CAG repeat of the DRPLA gene (group 1,

number of CAG repeat units > or = 66; group 2, number of CAG

repeat units < or = 65), we found strong inverse correlations

between the age at MRI and the areas of midsagittal structures

of the cerebellum and brainstem in group 1 but not in group 2.

Multiple regression analysis, however, revealed that both the

patient's age at MRI and the size of the expanded CAG repeat

correlated with the areas of midsagittal structures.

Involvement of the cerebral white matter as detected on T2-

weighted images was observed more frequently in patients

belonging to group 2 than in group 1 patients. Furthermore it

was demonstrated that high-intensity signals can be detected

on T2-weighted images of the cerebral white matter of

patients with a largely expanded CAG repeat (group 1) in their

thirties. These results suggest that patient age as well as the

size of the expanded CAG repeat are related to the degree of

atrophy of the brainstem and cerebellum, and the white matter

changes in patients with DRPLA.. 0; 0.

92. Kolb, F. P.; Arnold, G.; Lerch, R.; Straka, H.; Buttner Ennever, J.

Spatial distribution of field potential profiles in the cat

cerebellar cortex evoked by peripheral and central inputs.

Neuroscience. 1997 Dec; 81(4): 1155-81; ISSN: 0306-4522.

UNITED-STATES. The present study was designed to

characterize the spread of excitation within the frontal plane

of the cat cerebellar cortex following different types of

stimuli. In particular, experiments were performed to

determine whether the spread of excitation evoked by mossy

fibre inputs proceeds primarily along the parallel fibres

("beam-like" spread) or whether these inputs activate non-

propagated foci ("patches") in the cerebellar cortex. Field

potentials were recorded within a frontal plane as a medial to

lateral array at different depths in parallel tracks. The

recordings were made following electrical stimulation of

different forelimb nerves and functionally related areas of the

sensorimotor cortex as well as during passive paw movements.

The resulting spatial grid of responses provides discrete

spatio-temporal information reflecting the activation of

specific cerebellar afferents and the neuronal interactions

they evoke. The method employed demonstrates the spatial

distribution of the temporal sequence of excitability changes

throughout all the cerebellar cortical layers. In general, the

characteristics of the responses in the intermediate

cerebellar cortex depended on the source of the signals.

Activity patterns evoked by peripheral nerve stimulation

showed more clustered foci compared with those following

electrical stimulation of functionally related areas of the

sensorimotor cortex. The centrally evoked profiles were

generally more homogeneous. The largest number of foci were

observed following passive movements around the wrist joint.

The spread of excitation in the vertical direction was

evaluated by the spatial shift of the line of reversal of the

N3/P2-potential (zero-isopotential line). Lines of reversal for

peripherally-evoked activity patterns were approximately 90

microns closer to the molecular layer than those evoked by

central stimulation in animals in which recordings have been

performed in lobule Vc. The opposite was found for recordings

in lobule Vb, where potential reversals following peripheral

stimulation were located 40 microns deeper than those evoked

following central stimulation. Cortical inputs resulted in a

more proximal activation of lobule Vc Purkinje cell dendrites

than in lobule Vb. This type of input processing thus seems to

be lobule dependent. A beam-like spread of excitation could

not be demonstrated. For both climbing fibre and mossy fibre

afferent systems multiple foci were found in the frontal plane.

The foci due to mossy fibre activation arose from the granular

layer and expanded vertically to the molecular layer. For the

climbing fibre system the foci were restricted to the

molecular layer, where they merged to form a superficial band

of activation. Although the data presented in this paper favour

a focal distribution of activity, they do not exclude beam-like

propagation along the parallel fibres, because of the difficulty

of detecting this pattern in response to the stimuli. The

"beam"- and "patch"-like hypotheses need not be mutually

exclusive. Each could contribute to a specific stage of the

temporal-spatial processing in the cerebellar cortex in a

functional and task-specific manner.

93. Komuro, H.; Rakic, P. Distinct modes of neuronal migration in

different domains of developing cerebellar cortex. J-Neurosci.

1998 Feb 15; 18(4): 1478-90; ISSN: 0270-6474.

UNITED-STATES. As postmitotic neurons migrate to their final

destinations, they encounter different cellular

microenvironments, but functional responses of migrating

neurons to changes in local environmental cues have not been

examined. In the present study, we used a confocal microscope

on acute cerebellar slice preparations to examine real-time

changes in the shape of granule cells, as well as the mode and

rate of their migration as they transit different

microenvironments. The rate of granule cell movement is

fastest in the molecular layer, whereas their elongated

somata and long leading processes remain in close contact

with Bergmann glial fibers. Cell movement is slowest in the

Purkinje cell layer after granule cells detach from the surface

of Bergmann glia and the somata become transiently round,

whereas the leading processes considerably shorten.

Surprisingly, after entering the internal granular layer,

granule cells re-extend both their somata and leading

processes as they resume rapid movement independent of

Bergmann glial fibers. In this last phase of migration,

described here for the first time, most granule cells move

radially for >100 micron (a distance comparable to that

observed in the molecular layer) until they reach the deep

strata of the internal granular layer, where they become

rounded again and form synaptic contacts with mossy fiber

terminals. These observations reveal that migrating neurons

alter their shape, rate, and mode of movement in response to

local environmental cues and open the possibility for testing

the role of signaling molecules in cerebellar neurogenesis.

94. Koos, W. T.; Day, J. D.; Matula, C.; Levy, D. I. Neurotopographic

considerations in the microsurgical treatment of small

acoustic neurinomas. J-Neurosurg. 1998 Mar; 88(3): 506-12;

ISSN: 0022-3085.

UNITED-STATES. OBJECT: The authors studied the

relationships between tumor size, location, and topographic

position relative to the intact facial nerve bundles in acoustic

neurinomas to determine the influence of these factors on

hearing preservation postoperatively. Consistent topographic

relationships were found. METHODS: Four hundred fifty-two

patients with acoustic neurinoma treated via a retrosigmoid

approach were analyzed with respect to hearing preservation

and facial nerve function. One hundred fifteen tumors were

identified as small and were categorized as Grades I and II.

Patients with Grade I tumors, that is, purely intracanalicular

lesions, all had good hearing preoperatively, defined by a less

than 50-dB pure tone average and 50% speech discrimination

score. All 14 Grade I tumors were removed, resulting in

preservation of the patient's hearing by these criteria. There

were no particular topographic anatomical relationships

associated with these tumors that affected hearing

preservation. Grade II tumors, defined as those protruding into

the cerebellopontine angle without contacting the brainstem,

were found in 101 patients and were divided by size into two

grades: IIA (< 1 cm) and IIB (1-1.8 cm). In 90 patients with

Grade IIA tumors, 72 (89%) of 81 who had preserved hearing

preoperatively maintained it postoperatively, and in the 11

patients with Grade IIB tumors, six of whom had good hearing

preoperatively, four (67%) had preserved hearing

postoperatively. Six morphological types were identified based

on their neurotopographic relationships to the elements of the

vestibulocochlear nerve. CONCLUSIONS: Hearing preservation

postsurgery by tumor type was as follows: 1A, 92%; 1B, 88%;

1C, 100%; 2A, 83%; 2B, 92%; and 3, 57%. Combined, this

represents a hearing preservation rate of 87% after surgical

treatment of Grade II acoustic neurinomas. Full nerve function

was maintained in 88% of patients with anatomically

preserved facial nerves in both Grade I and II tumors. The

remaining 12% of patients retained partial function of the

facial nerve. Two patients in the series lost anatomical

integrity of the nerve due to surgery.

95. Kril, J. J.; Flowers, D.; Butterworth, R. F. Distinctive pattern of

Bergmann glial pathology in human hepatic encephalopathy.

Mol-Chem-Neuropathol. 1997 Aug; 31(3): 279-87; ISSN: 1044-

7393.

UNITED-STATES. Alzheimer type II astrocytosis is the

pathological hallmark of hepatic encephalopathy. These

astrocytes undergo a characteristic morphological change and,

in addition, lose immunoreactivity for glial fibrillary acidic

protein (GFAP). However, a previous study in the portacaval

shunted rat, a model of hepatic encephalopathy, revealed

increased rather than decreased GFAP immunoreactivity in

Bergmann glia, a specialized group of cerebellar astrocytes. In

the present study, sections of cerebellar vermis from 15

cirrhotic patients with hepatic encephalopathy and varying

degrees of Alzheimer type II astrocytosis were stained using

antisera to GFAP. The Bergmann glial cells did not show

altered GFAP immunoreactivity compared to controls. In

addition, the degree of GFAP immunoreactivity was not

correlated with the degree of Alzheimer type II change nor

related to the aetiology of the liver disease. These results

suggest a differential response of Bergmann glia in human

hepatic encephalopathy.. 0.

96. Kume, N.; Hayashida, K.; Cho, I. H.; Shimotsu, Y.; Nishioeda, Y.;

Matsunaga, N. Visualization of frontal postural hypoperfusion

in patients with Takayasu arteritis with upright 99Tcm-

HMPAO brain SPET. Nucl-Med-Commun. 1997 Oct; 18(10): 943-

50; ISSN: 0143-3636.

ENGLAND. Takayasu arteritis is a chronic inflammatory

angiopathy involving the cerebral arteries. We performed

upright and supine 99Tcm-HMPAO brain single photon emission

tomography (SPET) to investigate the cerebral perfusion

pattern in eight patients with Takayasu arteritis, and we

compared the results with those acquired using 123I-IMP and

acetazolamide in six patients. SPET images were evaluated

visually and semi-quantitatively. Hypoperfusion was visually

detected in all eight patients during the provocative upright

test with 99Tcm-HMPAO, and in three of six tested using

acetazolamide and 123I-IMP. Semiquantitative analysis

revealed that the mean cortical-to-cerebellar ratio in the

upright position was significantly changed compared to that in

the supine position in the right frontal area (from 0.86 +/-

0.07 to 0.91 +/- 0.09; P < 0.05). Change was also seen in the

left frontal area (from 0.85 +/- 0.08 to 0.91 +/- 0.08; P <

0.05). No significant change was seen in other cortical areas

with the upright test or in any areas with the acetazolamide

test. We postulate that reduced arterial compliance may cause

frontal postural hypoperfusion in patients with Takayasu

arteritis due to poor functioning of autoregulation and arterial

stenosis or occlusion. We conclude that the provocative

upright test with 99Tcm-HMPAO brain SPET can detect

abnormal patterns of cerebral perfusion in patients with

Takayasu arteritis that might be missed by brain SPET using

123I-IMP and acetazolamide.. 0; 0; 0; 51-43-4; 59-66-5.

97. Kurihara, H.; Hashimoto, K.; Kano, M.; Takayama, C.; Sakimura, K.;

Mishina, M.; Inoue, Y.; Watanabe, M. Impaired parallel fiber--

>Purkinje cell synapse stabilization during cerebellar

development of mutant mice lacking the glutamate receptor

delta2 subunit. J-Neurosci. 1997 Dec 15; 17(24): 9613-23;

ISSN: 0270-6474.

UNITED-STATES. The glutamate receptor delta2 subunit

(GluRdelta2) is specifically expressed in cerebellar Purkinje

cells (PCs) from early developmental stages and is selectively

localized at dendritic spines forming synapses with parallel

fibers (PFs). Targeted disruption of the GluRdelta2 gene leads

to a significant reduction of PF-->PC synapses. To address its

role in the synaptogenesis, the morphology and

electrophysiology of PF-->PC synapses were comparatively

examined in developing GluRdelta2 mutant and wild-type

cerebella. PCs in GluRdelta2 mutant mice were normally

produced, migrated, and formed spines, as did those in wild-

type mice. At the end of the first postnatal week, 74-78% of

PC spines in both mice formed immature synapses, which were

characterized by small synaptic contact, few synaptic

vesicles, and incomplete surrounding by astroglial processes,

eliciting little electrophysiological response. During the

second and third postnatal weeks when spines and terminals

are actively generated, the percentage of PC spines forming

synapses attained 98-99% in wild type but remained as low as

55-60% in mutants, and the rest were unattached to any nerve

terminals. As a result, the number of PF synapses per single-

mutant PCs was reduced to nearly a half-level of wild-type

PCs. Parallelly, PF stimulation less effectively elicited EPSCs

in mutant PCs than in wild-type PCs during and after the

second postnatal week. These results suggest that the

GluRdelta2 is involved in the stabilization and strengthening

of synaptic connectivity between PFs and PCs, leading to the

association of all PC spines with PF terminals to form

functionally mature synapses.. 0.

98. Kuwamura, M.; Ishida, A.; Yamate, J.; Kato, K.; Kotani, T.; Sakuma,

S. Chronological and immunohistochemical observations of

cerebellar dysplasia and vermis defect in the hereditary

cerebellar vermis defect (CVD) rat. Acta-Neuropathol-Berl.

1997 Dec; 94(6): 549-56; ISSN: 0001-6322.

GERMANY. Hereditary cerebellar vermis defect (CVD) rats, a

new neurological mutant, developed both cerebellar vermis

defect and cerebellar dysplasia. Developmental alterations in

the cerebellum of the CVD rats were studied chronologically

and immunohistochemically. The earliest architectural

abnormality was a maldevelopment of the inferior cerebellar

peduncle from embryonic day 17 (E17), leading to an indistinct

separation between the cerebellum and the pons. From E19, the

CVD rats lacked vermis development and, therefore, the

cerebellar hemispheres were fused. After birth, Purkinje cells

and external granule cells (EGCs) penetrated into the pontine

tissue, but retained their normal position until postnatal day

10. Cerebellar lamination began to be disturbed due to

abnormal perivascular aggregations of the EGCs, resulting in

convoluted and occasionally perivascular lamination. There

were no Bergmann glia in the heterotopic cerebellum of the

pons, and abnormally arranged Bergmann glia were observed in

the mildly disorganized cerebellar hemispheres.

Immunohistochemistry for calbindin revealed that abnormal

orientation of the Purkinje cells might be related to the

perivascular EGCs. Parvalbumin-immunopositive microneurons

were seen only in the disarranged molecular layers, and

synaptophysin-immunopositive cerebellar glomeruli were

present in the afflicted internal granular layers. These

findings suggest that perivascular EGCs may play an important

role in cerebellar dysplasia and the developmental plasticity

in the altered cerebellogenesis.. 0; 0; 0; 0; 0; 0.

99. Landsend, A. S.; Amiry Moghaddam, M.; Matsubara, A.; Bergersen, L.;

Usami, S.; Wenthold, R. J.; Ottersen, O. P. Differential

localization of delta glutamate receptors in the rat

cerebellum: coexpression with AMPA receptors in parallel

fiber-spine synapses and absence from climbing fiber-spine

synapses. J-Neurosci. 1997 Jan 15; 17(2): 834-42; ISSN: 0270-

6474.

UNITED-STATES. The delta 2 glutamate receptors are

prominently expressed in Purkinje cells and are thought to

play a key role in the induction of cerebellar long-term

depression. The synaptic and subsynaptic localization of delta

receptors in rat cerebellar cortex was investigated with

sensitive and high-resolution immunogold procedures. After

postembedding incubation with an antibody raised to a C-

terminal peptide of delta 2, high gold particle densities

occurred in all parallel fiber synapses with Purkinje cell

dendritic spines, whereas other synapses were consistently

devoid of labeling. Among the types of immunonegative

synapse were climbing fiber synapses with spines and parallel

fiber synapses with dendritic stems of interneurons. At the

parallel fiber-spine synapse, gold particles signaling delta

receptors were restricted to the postsynaptic specialization.

By the use of double labeling with two different gold particle

sizes, it was shown that delta and AMPA GluR2/3 receptors

were colocalized along the entire extent of the postsynaptic

specialization without forming separate domains. The

distribution of gold particles representing delta receptors was

consistent with a cytoplasmic localization of the C terminus

and an absence of a significant presynaptic pool of receptor

molecules. The present data suggest that the delta 2 receptors

are targeted selectively to a subset of Purkinje cell spines and

that they are coexpressed with ionotropic receptors in the

postsynaptic specialization. This arrangement could allow for

a direct interaction between the two classes of receptor.. 0;

0; 0; 0; 0.

100. Le Marec, N.; Stelz, T.; Delhaye Bouchaud, N.; Mariani, J.; Caston, J.

Effect of cerebellar granule cell depletion on learning of the

equilibrium behaviour: study in postnatally X-irradiated rats.

Eur-J-Neurosci. 1997 Nov; 9(11): 2472-8; ISSN: 0953-816X.

ENGLAND. To assess the role of the mossy fibre-granule cell

pathway in learning, the cerebellum of young DA/HAN strain

rats was irradiated to make the cortex completely or partially

agranular. The X-rays were delivered according to two

different schedules, between 5-14 postnatal days (early

group) and between 10-14 postnatal days (late group).

Histological controls at 35 days showed a mean loss of granule

cells of 96 +/- 1% in the early group and of 61 +/- 3% in the

late group. The irradiated animals were subjected, from day 23

to day 35, to daily sensorimotor training on a rotorod. The

scores and the strategy used (walking or hanging) by the rats

were noted. The results demonstrate that a partial loss of

granule cells due to a late X-irradiation schedule induced mild

motor disabilities but no learning deficit, the only problem

being difficulty in elaborating rapidly an efficient strategy to

solve a novel problem. A sub-total loss of the granule cells,

due to an early X-irradiation schedule, induced gross motor

disabilities and the animals used hanging > 90% of the time.

Due to the discrepancy between the learning abilities, which

were preserved at least in part, and the gross motor

impairments, the animals elaborated a novel strategy (jumping

from the beam), allowing them to escape the experimental

situation. This avoidance behaviour may be due to a decrease

of anxiety, a lack of behavioural inhibition and/or attentional

deficits that have been already observed in several other

examples of cerebellar abnormalities.

101. Lejeune, H.; Maquet, P.; Bonnet, M.; Casini, L.; Ferrara, A.; Macar, F.;

Pouthas, V.; Timsit Berthier, M.; Vidal, F. The basic pattern of

activation in motor and sensory temporal tasks: positron

emission tomography data. Neurosci-Lett. 1997 Oct 10; 235(1-

2): 21-4; ISSN: 0304-3940.

IRELAND. Positron emission tomography (PET) data were

obtained from subjects performing a synchronization task

(target duration 2700 ms). A conjunction analysis was run to

identify areas prominently activated both in this task and in a

temporal generalization task (target duration 700 ms) used

previously. The common pattern of activation included the

right prefrontal, inferior parietal and anterior cingulate

cortex, the left putamen and the left cerebellar hemisphere.

These areas are assumed to play a major role in time

processing, in relation to attention and memory mechanisms.

102. Lemmens Gruber, R.; Studenik, C.; Karkhaneh, A.; Heistracher, P.

Mechanism of sodium channel blockade in the cardiotoxic

action of emetine dihydrochloride in isolated cardiac

preparations and ventricular myocytes of guinea pigs. J-

Cardiovasc-Pharmacol. 1997 Nov; 30(5): 554-61; ISSN: 0160-

2446.

UNITED-STATES. Emetine is used in the therapy of special

forms of amebiasis and is abused as syrup of ipecac by persons

with bulimia. Severe cardiac side effects were reported. Thus

the intracellular microelectrode technique and the patch-

clamp technique in the cell-attached mode were used to study

the effects of emetine on the action potential and upstroke

velocity (Vmax) in papillary muscles and Purkinje fibers of

guinea pigs as well as on macroscopic and (S)-DPI 201-106-

modified and unmodified single-sodium-channel current (I(Na))

of guinea-pig ventricular myocytes. Emetine caused a tonic

block of Vmax and reduced I(Na) independent of frequency. Hill

plots were linear, with slopes ranging from 0.96 to 1.06,

suggestive of a first-order reaction. The current-voltage

relation was not influenced, indicating a voltage-independent

blockade of the sodium channels. The most prominent effects

were an increase of sweeps without activity, a decrease of the

fast component of the open-time distribution, an increase of

the slow component of the closed-time distribution, and a

reduction in the number of bursts per record. The amplitude of

the unitary current was not changed. From the results, we

conclude that I(Na) blockade contributes to the cardiotoxicity

of emetine.. 0; 0; 483-18-1.

103. Lenhoff, H. M.; Wang, P. P.; Greenberg, F.; Bellugi, U. Williams

syndrome and the brain. Sci-Am. 1997 Dec; 277(6): 68-73;

ISSN: 0036-8733.

UNITED-STATES. 9007-58-3.

104. Lester, D. S.; Olds, J. L.; Schreurs, B. G.; McPhie, D.; Bramham, C. R.;

Alkon, D. L. Incorporation of fluorescent lipids into living

rabbit hippocampal and cerebellar slices. Neuroimage. 1994

Nov; 1(4): 264-75; ISSN: 1053-8119.

UNITED-STATES. Incorporation of exogenously applied

fluorescent lipids into living cells was exploited to probe

cellular structure and function in living hippocampal and

cerebellar slices as assessed by fluorescent imaging

techniques and intracellular recording. Nitrobenzoxadiole-

phosphatidylcholine (NBD-PC) and BODIPY phorbol ester, in

vitro substrates of phospholipase activity and protein kinase

C, respectively, were incorporated and distributed into

specific cell populations. In the hippocampal slice, both probes

labeled the somata and proximal dendrites of pyramidal and

granule cells but were hetrogeneously distributed across the

different hippocampal fields. Changes in fluorescent

properties of NBD-PC in individual pyramidal cell and granule

cell somata were quantified upon challenge with a muscarinic

agonist known to modulate phospholipase A2 activity. In the

cerebellar slice, both probes labeled Purkinje cell bodies and

dendrites but only NBD-PC labeled stellate and granule cells.

The cellular and functional specificity of these fluorescent

lipid probes shows great promise for monitoring biochemical

events in complex neuronal systems with significant spatial

and temporal resolution.. 0; 0; 0; 0; 0; 0; 10199-89-0.

105. Li, H.; Mizuno, N. Direct projections from nucleus X to the external

cortex of the inferior colliculus in the rat. Brain-Res. 1997

Nov 7; 774(1-2): 200-6; ISSN: 0006-8993.

NETHERLANDS. Direct projections from nucleus X to the

external cortex of the inferior colliculus (ICe) were found in

the rat by the retrograde single- and double-labeling methods.

The projections are bilateral with a clear contralateral

dominance. Some of these projections are made by axon

collaterals of projection fibers from nucleus X to the

ventrobasal thalamus. On the other hand, projection fibers

from nucleus X to the cerebellum send no axon collaterals to

ICe.

106. Liu, H. G.; Mountz, J. M.; Inampudi, C.; San Pedro, E. C.; Deutsch, G. A

semiquantitative cortical circumferential normalization

method for clinical evaluation of rCBF brain SPECT. Clin-Nucl-

Med. 1997 Sep; 22(9): 596-604; ISSN: 0363-9762.

UNITED-STATES. The authors studied 33 normal patients who

ranged in age from 8 to 71 years to establish a normative data

base for young-age, middle-age, and older-age subjects using a

computer automated semi-quantitative cortical annular region

of interest (ROI) method. The data were grouped to obtain a

"young age-range" normative data base of mean age +/- 1 S.D. =

13.1 +/- 4.8 years (seven subjects with an age range of 6 to 20

years); a "middle age-range" normative data base of mean age

+/- 1 S.D. = 39 +/- 2.7 years (12 subjects with an age range of

35 to 43 years); and an "older age-range" normative data base

of mean age +/- 1 S.D. = 59.7 +/- 5.8 years (14 subjects with

an age range of 55 to 71 years). Normative values were

obtained for brain level parallel to and positioned at 3.5, 5.5,

and 7.5 cm above the canthomeatal (CM) line. The results show

that the average global rCBF indices (defined as

cortical/cerebellar ratios) for the young age-range group were

0.98, 0.99, 1.07; middle age-range group were 0.84, 0.86, and

0.88; and older age-range group were 0.86, 0.87 and 0.87 for

CM + 3.5 cm, CM + 5.5 cm, and CM + 7.5 cm, respectively. In

routine clinical studies, on more then 2,000 Tc-99m HMPAO

brain SPECT scans, the authors have employed this semi-

quantitative cortical circumferential normalization method of

analysis to accurately calculate indices representing cortical

blood flow values. This method also allows efficient

comparison of individual patient values to age-range matched

normal control groups to assist in disease diagnosis.. 0; 0.

107. Lucas, F. R.; Salinas, P. C. WNT-7a induces axonal remodeling and

increases synapsin I levels in cerebellar neurons. Dev-Biol.

1997 Dec 1; 192(1): 31-44; ISSN: 0012-1606.

UNITED-STATES. WNT factors play a key role in early

patterning of the embryo. However, expression of Wnt genes

after cell commitment suggests additional roles in later

developmental processes. We report here that Wnt-7a is

expressed in cerebellar granule cell neurons as they begin to

extend processes and form synapses. WNT-7a increases axonal

spreading and branching in cultured granule cells. Moreover,

WNT-7a increases the levels of synapsin I, a presynaptic

protein involved in synapse formation and function. Lithium

mimics WNT-7a in granule cells by inhibiting GSK-3beta, a

component of the WNT signaling pathway. These results

suggest a direct effect of WNT-7a in the regulation of

neuronal cytoskeleton and synapsin I in granule cell neurons.

We propose that WNT proteins have a novel function in the

formation of neuronal connections. Copyright 1997 Academic

Press.. 0; 0; 0; 63231-63-0; 7439-93-2.

108. Lujan, R.; Roberts, J. D.; Shigemoto, R.; Ohishi, H.; Somogyi, P.

Differential plasma membrane distribution of metabotropic

glutamate receptors mGluR1 alpha, mGluR2 and mGluR5,

relative to neurotransmitter release sites. J-Chem-Neuroanat.

1997 Oct; 13(4): 219-41; ISSN: 0891-0618.

NETHERLANDS. Two group I metabotropic glutamate receptor

subtypes, mGluR1 and mGluR5, have been reported to occur in

highest concentration in an annulus surrounding the edge of the

postsynaptic membrane specialisation. In order to determine

whether such a distribution is uniform amongst postsynaptic

mGluRs, their distribution was compared quantitatively by a

pre-embedding silver-intensified immunogold technique at

electron microscopic level in hippocampal pyramidal cells

(mGluR5), cerebellar Purkinje cells (mGluR1 alpha) and Golgi

cells (mGluR2). The results show that mGluR1 alpha, mGluR5

and mGluR2 each have a distinct distribution in relation to the

glutamatergic synaptic junctions. On dendritic spines, mGluR1

alpha and mGluR5 showed the highest receptor density in a

perisynaptic annulus (defined as within 60 nm of the edge of

the synapse) followed by a decreasing extrasynaptic (60-900

nm) receptor level, but the gradient of decrease and the

proportion of the perisynaptic pool (mGluR1 alpha,

approximately 50%; vs mGluR5, approximately 25%) were

different for the two receptors. The distributions of mGluR1

alpha and mGluR5 also differed significantly from simulated

random distributions. In contrast, mGluR2 was not closely

associated with glutamatergic synapses in the dendritic

plasma membrane of cerebellar Golgi cells and its distribution

relative to synapses is not different from simulated random

distribution in the membrane. The somatic membrane, the axon

and the synaptic boutons of the GABAergic Golgi cells also

contained immunoreactive mGluR2 that is not associated with

synaptic specialisations. In the hippocampal CA1 area the

distribution of immunoparticles for mGluR5 on individual

spines was established using serial sections. The results

indicate that dendritic spines of pyramidal cells are

heterogeneous with respect to the ratio of perisynaptic to

extrasynaptic mGluR5 pools and about half of the

immunopositive spines lack the perisynaptic pool. The

quantitative comparison of receptor distributions

demonstrates that mGluR1 alpha and mGluR5, but not mGluR2,

are highly compartmentalised in different plasma membrane

domains. The unique distribution of each mGluR subtype may

reflect requirements for different transduction and effector

mechanisms between cell types and different domains of the

same cell, and suggests that the precise placement of

receptors is a crucial factor contributing to neuronal

communication.. 0; 0; 0; 0; 0.

109. Maggi, G.; Varone, A.; Aliberti, F. Acute cerebellar ataxia in

children. Childs-Nerv-Syst. 1997 Oct; 13(10): 542-5; ISSN:

0256-7040.

GERMANY. Acute cerebellar ataxia is a benign syndrome

usually occurring after an acute febrile disease. In a few cases

neuroradiological investigations reveal cerebellar alterations.

Clinical and neuroradiological involvement of the brain stem

has rarely been reported in the literature. We present five

cases of acute cerebellar ataxia. In two cases the cerebellar

symptomatology was associated with neurological signs of

brain stem involvement. CT scans did not show any pathologic

findings in three patients. MRI disclosed cerebellar or brain

stem alterations in all the patients. Clinical and

neuroradiological findings allow differentiation of this

pathologic entity from other demyelinating or dysmyelinating

diseases. The value of MRI in detection and localization of the

lesions and in following their evolution is emphasized.

110. Majewska Michalska, E. Vascularization of the brain in guinea pig

III. Vascular architecture of the medula oblongata, pons, and

cerebellum. Folia-Morphol-Warsz. 1997; 56(1): 41-6; ISSN:

0015-5659.

POLAND. The blood vessels of the medulla oblongata and pons

are arranged into anterior (medial), lateral, and posterior

groups. Particular part of the brain receive also blood from

several sides (medial, lateral, posterior) what secures rich

capillary net and vascular loops. Venous blood is drained by

veins running in the same directions. The richest capillary

nets are found within brain stem nuclei. The cerebellum is

supplied by three cerebellar arteries.

111. Marini, A. M.; Spiga, G.; Mocchetti, I. Toward the development of

strategies to prevent ischemic neuronal injury. In vitro

studies. Ann-N-Y-Acad-Sci. 1997 Oct 15; 825: 209-19; ISSN:

0077-8923.

UNITED-STATES. Cerebellar granule cells in culture, which are

extremely vulnerable to excitotoxin glutamate or N-methyl-D-

aspartate (NMDA), were used to study mechanisms of neuronal

cell death and protection. Paradoxically, pretreatment of these

cells with subtoxic concentrations of NMDA markedly blocked

the neurotoxicity resulting from subsequent exposure to

glutamate or NMDA. The NMDA-mediated neuroprotection can be

antagonized by pretreatment of these cells with protein

synthesis inhibitors, suggesting an involvement of protein(s)

with neuroprotectant properties, most likely neurotrophic

factors. Because basic fibroblast growth factor (BFGF) is well

known to prevent neuronal cell death following mechanical or

chemical injury, we have tested whether NMDA increases the

synthesis of bFGF in cerebellar granule cells. NMDA elicited a

rapid and time-dependent increase in bFGF mRNA, suggesting

that availability of this trophic factor may play a role in the

NMDA-mediated neuroprotection.. 0; 0; 0; 0; 56-86-0; 6384-

92-5.

112. Martinez, G.; Di Giacomo, C.; Carnazza, M. L.; Sorrenti, V.; Castana,

R.; Barcellona, M. L.; Perez Polo, J. R.; Vanella, A. MAP2,

synaptophysin immunostaining in rat brain and behavioral

modifications after cerebral postischemic reperfusion. Dev-

Neurosci. 1997; 19(6): 457-64; ISSN: 0378-5866.

SWITZERLAND. Plasticity in the central nervous system after

cerebral ischemia is a controversial issue; focal cerebral

ischemia produces an area of infarction that is surrounded by

neurons that may respond to nearby damage by creating new

synapses. In the present study the expression of the

postsynaptic microtubule-associated protein 2 (MAP2) and the

presynaptic marker protein, synaptophysin, was investigated

by immunocytochemical techniques in the CA1 sector of

hippocampus and in cerebellum of rats made ischemic by

bilateral clamping of common carotid arteries and reperfused

for 7 and 30 days. In addition, ischemia-induced behavioral

alterations were also evaluated after 7 and 30 days of

reperfusion. The present study demonstrates a decreased

postsynaptic MAP2 immunoreactivity, representative of

neuronal loss, particularly in CA1 sector of hippocampus and

in cerebellum of ischemic rats reperfused for 7 days. After 30

days of reperfusion, MAP2 immunostaining was similar to

control. In the same brain sections an increased presynaptic

synaptophysin immunoreactivity has been observed only after

30 days of reperfusion. These data suggest compensatory

regenerative changes associated with synaptic remodelling

and are supported by behavioral recovery observed under the

same experimental conditions.. 0; 0.

113. Mascalchi, M.; Tosetti, M.; Plasmati, R.; Bianchi, M. C.; Tessa, C.;

Salvi, F.; Frontali, M.; Valzania, F.; Bartolozzi, C.; Tassinari, C.

A. Proton magnetic resonance spectroscopy in an Italian family

with spinocerebellar ataxia type 1. Ann-Neurol. 1998 Feb;

43(2): 244-52; ISSN: 0364-5134.

UNITED-STATES. Linkage and DNA analysis, magnetic

resonance (MR) imaging, and single-voxel proton MR

spectroscopy were obtained in 10 members of an Italian

kindred with spinocerebellar ataxia type 1 (SCA1). The size of

the basis pontis, cerebellar hemispheres, middle cerebellar

peduncles, and medulla oblongata were decreased in 4

members carrying the SCA1 gene, compared with 6 unaffected

subjects. Diffuse signal changes in the pons and cerebellum

were observed only in the carrier with the longest disease

duration and greatest disability. The N-

acetylaspartate/creatine ratio and the choline/creatine ratio

in the basis pontis were markedly decreased in 2 symptomatic

SCA1 carriers and moderately decreased in 2 asymptomatic

SCA1 carriers, compared with the unaffected family members

and a control group of 10 healthy volunteers. Minor decreases

in the N-acetylaspartate/creatine ratio and the normal

choline/creatine ratio were observed in the cerebellar

hemisphere of the SCA1 carriers. Reduction of the N-

acetylaspartate/creatine ratio, demonstrated by MR

spectroscopy in the pons, is likely to reflect a loss of neuronal

viability and might represent a biochemical marker of SCA1

more sensitive than brainstem and cerebellum atrophy and

signal changes shown by MR imaging.. 56-84-8; 57-00-1; 62-

49-7; 6917-35-7; 9007-49-2; 997-55-7.

114. Mateo, J.; Garcia Lecea, M.; Miras Portugal, M. T.; Castro, E. Ca2+

signals mediated by P2X-type purinoceptors in cultured

cerebellar Purkinje cells. J-Neurosci. 1998 Mar 1; 18(5):

1704-12; ISSN: 0270-6474.

UNITED-STATES. We have studied [Ca2+]i signals elicited by

extracellular ATP in cultured cells from postnatal day 7-8 rat

cerebellum using single-cell fluorescence microscopy and

fura-2. Putative Purkinje cells selected under phase contrast

by size and characteristic cytoplasm appearance were uniquely

identified by selective labeling with anti-calbindin antibodies.

Extracellularly applied ATP (50 microM) evoked fast [Ca2+]i

rises revealed by a rapid and transient increase in fura-2

F340/F380 ratio in all Purkinje cells tested, whereas granule

cells failed to show a response to ATP. The mean [Ca2+]i

increase was approximately 400 nM, comparable to that

obtained after glutamate stimulation. The response to ATP

was completely abolished by removal of extracellular Ca2+

with EGTA. Conversely, an increased extracellular Mn2+ entry

pathway was activated by ATP stimulation. These results

indicate that the effect of ATP is mediated by an ionotropic

P2X receptor. The action of ATP was mimicked by the analog

2-methylthio-adenosine 5'-triphosphate with similar efficacy

but almost half its potency (EC50, 10.6 +/- 0.7 vs 21.7 +/- 1.9

&mgr;M). Other purinergic compounds tested, such as

adenosine(5')-tetraphospho-(5')adenosine,

adenosine(5')pentaphospho-(5')adenosine, adenosine 5'-(alpha,

beta-methylene) triphosphate, UTP, and adenosine, were

completely inactive in eliciting [Ca2+]i responses. The

purinoceptor antagonists suramin and pyridoxalphosphate-6-

azophenyl-2', 4'disulphonic acid effectively blocked the

responses elicited by ATP. Our results demonstrate for the

first time the presence of functional ionotropic P2X

purinoceptors in the cerebellar Purkinje cells and indicate

that their pharmacology is similar to receptors formed by

P2X2 subunit oligomers.. 0; 0; 0; 145-63-1; 56-65-5; 7440-

70-2; 96314-98-6.

115. Mathis, L.; Bonnerot, C.; Puelles, L.; Nicolas, J. F. Retrospective

clonal analysis of the cerebellum using genetic laacZ/lacZ

mouse mosaics. Development. 1997 Oct; 124(20): 4089-104;

ISSN: 0950-1991.

ENGLAND. Analysis of lacZ neuronal clones in the mouse

cerebellum demonstrates genealogical independence of the

primary and secondary germinal epithelia (PGE and SGE) from

early development. PGE precursors and their neuronal

descendants are organised into two polyclonal groups of

similar sizes that exhibit parasagittal patterning and

generally respect the midline. The relationship between these

two groups cannot be traced back in time to less than 80

independent cells, which were probably recruited following a

period of non-coherent growth that distributes unrelated cells

into distinct territories of the neural tube. A lateromedial

clonal organisation is observed in the mature cerebellum,

suggesting the existence of many small parasagittal domains

of clonal restriction and/or of cell dispersion in the

rostrocaudal but not in the mediolateral dimension. The

organisation is orthogonal with respect to the cellular

organisation in the neural tube as is the genetic organisation.

Cellular and genetic patterning of the cerebellum therefore

share similarities. A possible hypothesis is that distinct cell

behaviours create the different clonal domains observed in

this study and that the cellular and genetic organisation of the

cerebellum are coordinated.

116. Matsui, T. [Orphan nuclear receptor ROR alpha in cerebellum].

Tanpakushitsu-Kakusan-Koso. 1997 Oct; 42(13): 2039-48;

ISSN: 0039-9450.

JAPAN. 0; 0; 0; 0; 0.

117. Matsuura, T.; Sasaki, H.; Tashiro, K. Atypical MR findings in

Wilson's disease: pronounced lesions in the dentate nucleus

causing tremor. J-Neurol-Neurosurg-Psychiatry. 1998 Feb;

64(2): 161; ISSN: 0022-3050.

ENGLAND. 7440-50-8.

118. Matsuzaki, R.; Kyuhou, S. Pontine neurons which relay projections

from the superior colliculus to the posterior vermis of the

cerebellum in the cat: distribution and visual properties.

Neurosci-Lett. 1997 Oct 31; 236(2): 99-102; ISSN: 0304-3940.

IRELAND. Extracellular unit recording revealed that the

dorsolateral pontine nucleus (DLPN) and nucleus reticularis

tegmenti pontis (NRTP) of the cat constituted pontine relays

for transmission of visual information from the superior

colliculus (SC) to the posterior vermis (lobules VI and VII) of

the cerebellum. The relay neurons in DLPN/NRTP responded to

moving visual stimuli with large receptive fields (23-75

degrees ) which occupied mainly the contralateral hemifield

including the fovea. These neurons were usually more

responsive to large-sized stimuli than to discrete-spot

stimuli, had direction selectivity, and showed preference to

visual motion at a relatively high speed. No clear differences

in visual properties were observed between DLPN and NRTP.

After a local injection of lidocaine into SC, the visual

responses in DLPN/NRTP transiently disappeared, indicating

that DLPN/NRTP received the visual inputs through SC.

119. Mauceri, L.; Ruggieri, M.; Pavone, V.; Rizzo, R.; Sorge, G.

Craniofacial anomalies, severe cerebellar hypoplasia,

psychomotor and growth delay in a child with congenital

hypothyroidism [letter]. Clin-Dysmorphol. 1997 Oct; 6(4): 375-

8; ISSN: 0962-8827.

ENGLAND. We describe a 4-year-old boy affected by congenital

hypothyroidism (CH) with the unusual association of

brachycephaly, large and poorly structured ears, bilateral

convergent strabismus, pectus carinatum and slight scoliosis,

psychomotor delay, growth retardation and a severe hypoplasia

of the right cerebellar hemisphere and vermis. Given the

finding of unilateral cerebellar pathology this unusual

association might be explained by an insult in utero--more

environmental than genetic. However, to the best of our

knowledge, a relationship between CH and cerebellar

anomalies has not been previously reported.

120. McDonough, S. I.; Lampe, R. A.; Keith, R. A.; Bean, B. P. Voltage-

dependent inhibition of N- and P-type calcium channels by the

peptide toxin omega-grammotoxin-SIA. Mol-Pharmacol. 1997

Dec; 52(6): 1095-104; ISSN: 0026-895X.

UNITED-STATES. We studied the mechanism by which the

peptide omega-grammotoxin-SIA inhibits voltage-dependent

calcium channels. Grammotoxin at concentrations of > 50 nM

completely inhibited inward current carried by 2 mM barium

through P-type channels in rat cerebellar Purkinje neurons

when current was elicited by depolarizations up to +40 mV.

However, outward current (carried by internal cesium) elicited

by depolarizations to > +100 mV was either unaffected or

enhanced in the presence of toxin. Tail current activation

curves showed that grammotoxin shifted the steady state

voltage dependence of channel activation by approximately +40

mV. Activation in the presence of toxin was far slower in

addition to having altered voltage dependence. Grammotoxin

also inhibited N-type calcium channels in rat and frog

sympathetic neurons, with changes in channel voltage

dependence and kinetics nearly identical to those of P-type

channels. Experiments with monovalent ions as the only charge

carriers showed that toxin effects on channel activation and

kinetics depended on voltage, not on direction of current flow

or on the current-carrying ion. Repeated trains of large

depolarizations relieved toxin inhibition, as if toxin affinity

for activated channels were low. The effects of grammotoxin

on gating of P-type channels are very similar to those of

omega-Aga-IVA, but combined application of the two toxins

showed that grammotoxin binding is not prevented by

saturating binding of omega-Aga-IVA. We conclude that

grammotoxin potently inhibits both P-type and N-type

channels by impeding channel gating and that grammotoxin

binds to distinct or additional sites on P-type channels

compared with omega-Aga-IVA.. 0; 0; 0; 0; 0; 0.

121. Migheli, A.; Piva, R.; Wei, J.; Attanasio, A.; Casolino, S.; Hodes, M.

E.; Dlouhy, S. R.; Bayer, S. A.; Ghetti, B. Diverse cell death

pathways result from a single missense mutation in weaver

mouse. Am-J-Pathol. 1997 Dec; 151(6): 1629-38; ISSN: 0002-

9440.

UNITED-STATES. Neuronal death affects selectively granule

cell precursors of the cerebellum and the dopaminergic

neurons of midbrain in the weaver mutant mouse. The weaver

phenotype is associated with a missense mutation in the gene

coding for the GIRK2 potassium channel, which results in

chronic depolarization. Using DNA gel electrophoresis, electron

microscopy (EM), the in situ end-labeling (ISEL) technique at

the light and EM level, and immunohistochemistry for

apoptosis-related proteins c-Jun and proliferating cell nuclear

antigen (PCNA), we have investigated the mechanisms of cell

death in cerebellum and substantia nigra. Between postnatal

day P1 and P21, in the external germinal layer of the

cerebellum, most degenerating granule cell precursors were

found to aggregate to form clusters. Degenerating cells

exhibited strong nuclear staining for ISEL, c-Jun, and PCNA and

had a typical apoptotic morphology by EM. Increased c-Jun and

ISEL staining were also occasionally seen in Purkinje cells.

Between P14 and P21, when dopaminergic neurons start to

degenerate, staining for ISEL, c-Jun, and PCNA in weaver

substantia nigra was the same as in controls. By EM, however,

we found only in weaver mice numerous dopaminergic cells

that showed extensive vacuolar and autophagic changes of

cytoplasm, preservation of membrane and organelle integrity,

and absence of chromatin condensation or DNA fragmentation

by EM-ISEL. The combination of vacuolar and autophagic

changes identifies a novel type of non-necrotic, nonapoptotic

cell death. After biochemical analysis of DNA, a clear-cut

laddering, suggestive of oligonucleosomal fragmentation, was

present in samples from weaver cerebellum. Cell death

diversity appears to be influenced by specific features of

target cells. These findings may be relevant for understanding

the mechanisms of cell death in neurodegenerative diseases..

EC 1.14.16.2; 0; 0; 9007-49-2.

122. Miller, T. M.; Moulder, K. L.; Knudson, C. M.; Creedon, D. J.;

Deshmukh, M.; Korsmeyer, S. J.; Johnson, EM Jr. Bax deletion

further orders the cell death pathway in cerebellar granule

cells and suggests a caspase-independent pathway to cell

death. J-Cell-Biol. 1997 Oct 6; 139(1): 205-17; ISSN: 0021-

9525.

UNITED-STATES. Dissociated cerebellar granule cells

maintained in medium containing 25 mM potassium undergo an

apoptotic death when switched to medium with 5 mM

potassium. Granule cells from mice in which Bax, a

proapoptotic Bcl-2 family member, had been deleted, did not

undergo apoptosis in 5 mM potassium, yet did undergo an

excitotoxic cell death in response to stimulation with 30 or

100 microM NMDA. Within 2 h after switching to 5 mM K+, both

wild-type and Bax-deficient granule cells decreased glucose

uptake to <20% of control. Protein synthesis also decreased

rapidly in both wild-type and Bax-deficient granule cells to

50% of control within 12 h after switching to 5 mM potassium.

Both wild-type and Bax -/- neurons increased mRNA levels of

c-jun, and caspase 3 (CPP32) and increased phosphorylation of

the transactivation domain of c-Jun after K+ deprivation.

Wild-type granule cells in 5 mM K+ increased cleavage of

DEVD-aminomethylcoumarin (DEVD-AMC), a fluorogenic

substrate for caspases 2, 3, and 7; in contrast, Bax-deficient

granule cells did not cleave DEVD-AMC. These results place

BAX downstream of metabolic changes, changes in mRNA

levels, and increased phosphorylation of c-Jun, yet upstream

of the activation of caspases and indicate that BAX is required

for apoptotic, but not excitotoxic, cell death. In wild-type

cells, Boc-Asp-FMK and ZVAD-FMK, general inhibitors of

caspases, blocked cleavage of DEVD-AMC and blocked the

increase in TdT-mediated dUTP nick end labeling (TUNEL)

positivity. However, these inhibitors had only a marginal

effect on preventing cell death, suggesting a caspase-

independent death pathway downstream of BAX in cerebellar

granule cells.. EC 2.7.10.-; EC 2.7.10.-; EC 3.4.22; 0; 0; 0; 0;

6384-92-5.

123. Molinari, M.; Grammaldo, L. G.; Petrosini, L. Cerebellar

contribution to spatial event processing: right/left

discrimination abilities in rats. Eur-J-Neurosci. 1997 Sep;

9(9): 1986-92; ISSN: 0953-816X.

ENGLAND. Recently, we demonstrated the involvement of

cerebellar circuits in the procedural components of spatial

information processing by testing hemicerebellectomized

(HCbed) rats in classical spatial paradigms, such as the Morris

Water Maze and the water T-maze. Since procedural

components are strongly present in these tests, an impairment

also in processing more abstract spatial information, linked to

'where an object is' rather than to 'how to find it', could be

hidden by the severe procedural deficits. On this basis, we

investigated the influence of cerebellar lesions on spatial

abilities strictly reducing procedural variables by employing

an active avoidance task, first without and then with a request

for right/left discrimination. In the two-way active avoidance

task without spatial requests, controls and cerebellar

operated rats developed active avoidance responses which

were not statistically different, demonstrating that this kind

of associative learning is not significantly affected by

hemicerebellectomy (HCb). A second experimental group of

cerebellar lesioned rats was tested in a modified version of

this basic paradigm in which a right/left discrimination

request was added. This group displayed severe deficits, which

even in the last testing sessions prevented them from

performing comparably to the control animals. Reversal of the

rewarded choice, even if it affected the performances of both

controls and operated rats in the first inversion trials,

elicited the lowest number of correct responses in HCbed rats

throughout the entire spatial reversal learning, suggesting a

severe deficit in the ability to change an initially learned

behaviour. These results demonstrate that, beside having a

marked impairment in facing procedural components of spatial

processing, cerebellar lesioned rats are severely defective

also in right/left discrimination tasks, suggesting a role of

cerebellar networks also in the discriminative spatial

information processing.

124. Molinari, M.; Leggio, M. G.; Solida, A.; Ciorra, R.; Misciagna, S.;

Silveri, M. C.; Petrosini, L. Cerebellum and procedural learning:

evidence from focal cerebellar lesions. Brain. 1997 Oct; 120(

Pt 10): 1753-62; ISSN: 0006-8950.

ENGLAND. The aim of the present study was to investigate the

influence of focal cerebellar lesions on procedural learning.

Eight patients with cerebellar lesions and six control subjects

were tested in a serial reaction-time task. A four-choice

reaction-time task was employed in which the stimuli

followed (or not) a sequence repeated 10 times, with the

subjects aware (or not) of the item sequence. Learning was

manifested by the reduction in response latency over the

sequential blocks. Acquisition of declarative knowledge of the

sequence was also tested. Reaction times displayed by

patients with cerebellar lesions, even though they tended to be

longer than those of control subjects in all testing conditions,

significantly differed from control subjects only when the

stimuli were presented in sequence. The reaction times in

sequential trials were still statistically significant when

simple motor response times were taken into account.

Cerebellar patients were also significantly impaired in

detecting and repeating the sequence. On the other hand, when

the sequence was learned before testing, motor performances

were significantly improved in all subjects. These data

indicate that cerebellar lesions induce specific impairment in

the procedural learning of a motor sequence and suggest a role

of the cerebellar circuitry in detecting and recognizing event

sequences.

125. Monsell, E. M.; Cody, D. D.; Spickler, E.; Windham, J. P.

Segmentation of acoustic neuromas with magnetic resonance

imaging and Eigen image filtering. Am-J-Otol. 1997 Sep; 18(5):

602-7; ISSN: 0192-9763.

UNITED-STATES. OBJECTIVE: This study aimed to determine

whether magnetic resonance imaging with Eigen image

filtering can segment acoustic neuromas as a preliminary

requirement to the development and validation of a volumetric

method of measuring tumor size and growth using Eigen image

filtering. STUDY DESIGN: This was an observational study.

SETTING: The study was performed in an academic,

comprehensive multi-specialty group practice. PATIENTS:

Patients were a convenience sample of adults of both sexes

who had acoustic neuromas identified by magnetic resonance

imaging. Tumors ranged widely in size. INTERVENTION:

Magnetic resonance imaging with digital image analysis using

Eigen image filtering was the intervention. MAIN OUTCOME

MEASURE: Observation and analysis of magnetic resonance

images was the main outcome measure. RESULTS: The ability

of magnetic resonance imaging with Eigen image filtering to

segment acoustic neuromas of various sizes and shapes is

illustrated. CONCLUSIONS: Magnetic resonance imaging with

digital image analysis using Eigen image filtering is a

promising method for volumetric measurement of acoustic

neuroma size and growth. The potential for acoustic neuromas

to grow may be underestimated by linear methods because of

their relative lack of precision and of the geometric error that

occurs in representing the volumetric growth of a three-

dimensional tumor as a linear diameter.

126. Morara, S.; Marcotti, W.; Provini, L.; Rosina, A. Neuropeptide Y

(NPY) expression is up-regulated in the rat inferior olive

during development. Neuroreport. 1997 Dec 1; 8(17): 3743-7;

ISSN: 0959-4965.

ENGLAND. The aim of this study was to analyse the

developmental expression of the neuropeptide Y (NPY) in the

rat inferior olivary (IO) complex by immunoperoxidase and

immunofluorescence techniques. The spatial distribution of

NPY-immunoreactivity (IR) did not vary during development,

whereas NPY-IR intensity levels varied significantly. The peak

of NPY-IR expression occurred during the second postnatal

week, but differed in intensity in individual IO subnuclei, the

highest levels being present in the dorsal fold of the dorsal

accessory olive and in the ventro-lateral outgrowth. In the

adult, NPY-IR could only be rescued in colchicine pretreated

animals, but its distribution overlapped the one found during

development. These findings show that NPY-IR is transiently

up- regulated, during development, in specific compartments

of the IO complex, and that the peptide is rescued in the same

specific olivocerebellar compartments in the adult. These

observations are here taken to support the hypothesis that NPY

may exert different trophic-differentiating and/or

neuromodulatory roles during development, when its

expression is transiently up-regulated, or at adult stages,

when it can be rescued, according to the different biological

contexts.. 0.

127. Mostofsky, S. H.; Mazzocco, M. M.; Aakalu, G.; Warsofsky, I. S.;

Denckla, M. B.; Reiss, A. L. Decreased cerebellar posterior

vermis size in fragile X syndrome: correlation with

neurocognitive performance. Neurology. 1998 Jan; 50(1): 121-

30; ISSN: 0028-3878.

UNITED-STATES. We examined whether posterior vermis size

is smaller in individuals with fragile X syndrome (fra X) than

in control subjects and whether this decreased size is

associated with cognitive performance. Cognitive and

behavioral dysfunctions have been identified in fra X; however,

underlying neuropathogenic mechanisms remain unclear. MRI

was used to investigate the posterior fossa in 32 males with

fra X, 28 males with other causes of cognitive disability (CD),

and 38 males with normal development (ND) as well as and in

37 females with fra X and 53 female control subjects. Among

females with fra X, neurocognitive correlates of posterior

vermis size were examined. Posterior vermis size (cross-

sectional area) in males with fra X was significantly smaller

compared with CD and ND groups, particularly when corrected

for intracranial area. Posterior vermis size corrected for

intracranial area was significantly smaller in females with

fra X compared with control subjects. Compared with males

with fra X and non-fra X control subjects, posterior vermis

size in females with fra X was intermediate. After

statistically removing the effect of mean parental IQ,

posterior vermis size predicted a significant proportion of the

variance (10 to 23%) of performance on full-scale, verbal, and

performance IQ; block design; categories achieved on the

Wisconsin Card Sorting Test; and the Rey inventory score. The

size of the posterior vermis is significantly decreased in fra

X, more so in males than in females. In females with fra X,

posterior vermis size predicts performance on selected

cognitive measures.

128. Mourre, C.; Fournier, C.; Soumireu Mourat, B. Apamin, a blocker of

the calcium-activated potassium channel, induces

neurodegeneration of Purkinje cells exclusively. Brain-Res.

1997 Dec 19; 778(2): 405-8; ISSN: 0006-8993.

NETHERLANDS. Following acute intracerebroventricular

injections of 1 ng of apamin and chronic apamin infusion (0.4

ng/microl, 0.5 microl/h, 14 days), the rat brains exhibited

bilateral damage only in the cerebellum. The argyrophilic cells

were Purkinje cells in copula pyramis, flocculus,

paraflocculus, and paramedian lobules. These data demonstrate

that the inactivation of small conductance Ca2+-activated K+

channels by apamin induces a non-limbic neurodegeneration..

0; 24345-16-2; 7440-70-2.

129. Muller, Y. L.; Reitstetter, R.; Yool, A. J. Regulation of Ca2+-

dependent K+ channel expression in rat cerebellum during

postnatal development. J-Neurosci. 1998 Jan 1; 18(1): 16-25;

ISSN: 0270-6474.

UNITED-STATES. Potassium channels govern duration and

frequency of excitable membrane events and may regulate

signals that are important in neuronal development. This study

assesses the developmental expression of the large

conductance Ca2+-dependent K+ channel in vivo and in vitro in

rat cerebellum. In vivo, transcript levels for the Ca2+-

dependent K+ channel (KCa) were shown by Northern analysis

to increase during development, whereas transcript levels for

the voltage-gated K+ channel Kv3.1, a delayed rectifier (KD),

remained relatively constant. A comparable pattern was

demonstrated by expression in Xenopus oocytes of poly(A)-

enriched RNA isolated from postnatal rat cerebella. In

cerebellar cultures, increased external K+ provided a simple

manipulation of cell excitability that influenced KCa

transcript levels during development. With low external K+

(5.3 mM), the levels of KCa channel transcript (assessed by

semiquantitative PCR) remained constant throughout

development. However, in culture medium that supported

significant dendritic outgrowth (10 mM extracellular K+), an

upregulation of KCa transcript level was observed similar to

that seen in vivo. Tetraethylammonium (TEA; 1 mM) similarly

enhanced KCa expression, suggesting that depolarizing stimuli

increased KCa expression. The stimulatory effects of

increased K+ or TEA on KCa expression required extracellular

Ca2+ and were abolished in low external calcium (0.1 mM,

buffered with EGTA), although morphological development and

survival were not impaired. The regulation of KCa channel

expression by depolarization and Ca2+ entry provides evidence

of a logical feedback mechanism governing Ca2+ signals that

may be significant in cerebellar development.. EC 5.2.1.8; 0; 0;

0; 0; 0; 66-40-0; 7440-09-7; 7440-70-2.

130. Murata, Y.; Yamaguchi, S.; Kawakami, H.; Imon, Y.; Maruyama, H.;

Sakai, T.; Kazuta, T.; Ohtake, T.; Nishimura, M.; Saida, T.; Chiba,

S.; Oh, i. T.; Nakamura, S. Characteristic magnetic resonance

imaging findings in Machado-Joseph disease. Arch-Neurol.

1998 Jan; 55(1): 33-7; ISSN: 0003-9942.

UNITED-STATES. OBJECTIVE: To clarify the characteristic

magnetic resonance imaging (MRI) findings in patients with

Machado-Joseph disease (MJD) diagnosed by genetic analysis.

PATIENTS AND METHODS: Using MRI, we examined 31 patients

genetically diagnosed as having MJD, 20 patients with sporadic

olivopontocerebellar atrophy, and 26 control subjects.

RESULTS: The MRIs of patients with MJD disclosed remarkably

reduced width of the superior cerebellar peduncles, atrophy in

the frontal and temporal lobes, diminished transverse

diameter of the globus pallidus, and decreased anteroposterior

and transverse diameters of the pons, which correlated with

the width of the middle cerebellar peduncle. The width of the

superior cerebellar peduncles also correlated with the

diameter of the dentate or red nucleus in patients with MJD,

but not in controls or in patients with sporadic

olivopontocerebellar atrophy. On T2- and/or proton-weighted

axial MR imaging, a high signal intensity in the transverse

pontine fibers was observed in 14 (45.2%) of 31 patients with

MJD and in all patients with sporadic olivopontocerebellar

atrophy, but not in any controls. CONCLUSION: Affected

afferent and efferent cerebellar tracts and atrophy of the

frontal and temporal lobes and globus pallidus are

characteristics of MRI of patients with MJD.

131. Nagashima, K. A review of experimental methylmercury toxicity

in rats: neuropathology and evidence for apoptosis [see

comments]. Toxicol-Pathol. 1997 Nov; 25(6): 624-31; ISSN:

0192-6233.

Note: Comment in: Toxicol Pathol 1997 Nov-Dec;25(6):632-4.

UNITED-STATES. As an animal model for examining the

pathogenicity of human organic mercury intoxication, rats

have been used for the reproduction of human neurologic

diseases. Rats experimentally exposed to methylmercury

chloride showed clinical signs of neurologic dysfunction

characterized by ataxic behavior. Neuropathology of the

diseased animals consisted of lesions such as: (a) degeneration

of the peripheral nerve and sensory root nerve with

preservation of the motor root nerve; (b) degeneration of the

posterior funiculus of the spinal cord; and (c) degeneration of

cerebellar granule cells with preservation of Purkinje cells.

These findings suggest the human neuropathology of this

toxicity. The degeneration was characterized by nerve fiber

damage or neuronal cell death accompanied by astrocytic

gliosis and activated macrophages or microglias. For the

cerebellar granule cells, the mechanism of neuronal cell death

was shown to be apoptosis. This fact was verified by

histologic and ultrastructural findings as well as by in situ

nick-end labeling and electrophoretic methods. Evidence of

apoptosis involvement in cerebellar degeneration would

provide a new viewpoint from which to analyze the selected

degeneration of the nervous system in neurotoxicology.. 0;

9007-49-2.

132. Naudon, L.; Delfs, J. M.; Clavel, N.; Lorden, J. F.; Chesselet, M. F.

Differential expression of glutamate decarboxylase messenger

RNA in cerebellar Purkinje cells and deep cerebellar nuclei of

the genetically dystonic rat. Neuroscience. 1998 Feb; 82(4):

1087-94; ISSN: 0306-4522.

UNITED-STATES. The genetically dystonic rat exhibits a motor

syndrome that closely resembles the human disease,

generalized idiopathic dystonia. Although in humans dystonia

is often the result of pathology in the basal ganglia, previous

studies have revealed electrophysiological abnormalities and

alterations in glutamate decarboxylase, the synthetic enzyme

for GABA, in the cerebellum of dystonic rats. In this study, we

further characterized the alterations in cerebellar GABAergic

transmission in these mutants by examining the expression of

the messenger RNA encoding glutamate decarboxylase (67000

mol. wt) with in situ hybridization histochemistry at the

single cell level in Purkinje cells and neurons of the deep

cerebellar nuclei. Glutamate decarboxylase (67000 mol. wt)

messenger RNA levels were increased in the Purkinje cells and

decreased in the deep cerebellar nuclei of dystonic rats

compared to control littermates, suggesting opposite changes

in GABAergic transmission in Purkinje cells and in their target

neurons in the deep cerebellar nuclei. In contrast, levels of

glutamate decarboxylase (67000 mol. wt) messenger RNA in

the pallidum, and of enkephalin messenger RNA in the

striatum, were unaffected in dystonic rats. The data indicate

that both the Purkinje cells and GABAergic neurons of the deep

cerebellar nuclei are the site of significant functional

abnormality in the dystonic rat.. EC 4.1.1.15; 0; 0.

133. Nehru, B.; Dua, R.; Iyer, A. Effect of selenium on lead-induced

alterations in rat brain. Biol-Trace-Elem-Res. 1997 Jun; 57(3):

251-8; ISSN: 0163-4984.

UNITED-STATES. The effects of lead (Pb) and selenium (Se)

interactions on central nervous system (CNS) functions were

seen in adult rats by both biochemical and histologic

pathological alterations. Pb administration of 20 mg/kg body

wt for 8 wk showed degenerative changes only in the cerebral

cortex. The changes in the cerebellar regions were not

significant. Biochemically a marked decrease in the DNA, RNA,

and protein content was seen following lead treatment. These

decreases were significant in both the regions of the brain.

During the concomitant administration of Pb and Se, the

alterations in the transverse section of cerebral cortex

showed only marginal changes. The values of DNA and RNA

content showed significant improvement in both regions of the

brain compared to the Pb treated group.. 0; 63231-63-0;

7439-92-1; 7782-49-2; 9007-49-2.

134. Nespoli, L.; Lascari, C.; Maccario, R.; Nosetti, L.; Broggi, U.;

Locatelli, F.; Binda, S.; Gaudio, F.; Casalone, R.; Bosi, F. The

Hoyeraal-Hreidarsson syndrome: the presentation of the

seventh case [letter]. Eur-J-Pediatr. 1997 Oct; 156(10): 818-

20; ISSN: 0340-6199.

GERMANY. 0.

135. Nieto Bona, M. P.; Garcia Segura, L. M.; Torres Aleman, I.

Transynaptic modulation by insulin-like growth factor I of

dendritic spines in Purkinje cells. Int-J-Dev-Neurosci. 1997

Oct; 15(6): 749-54; ISSN: 0736-5748.

ENGLAND. Purkinje cells synthesize insulin-like growth factor

I and express insulin-like growth factor I receptors during

their entire life. An additional source of insulin-like growth

factor I for these cells is provided by climbing fiber afferents

originating in the inferior olive nucleus. Recently we found

that insulin-like growth factor I from the inferior olive is

necessary for motor learning processes probably involving

Purkinje cell synaptic plasticity. We now studied whether

inferior olive insulin-like growth factor I influences the

synaptic structure of Purkinje cells, because changes in

synaptic morphology are related to neuronal plasticity events.

We injected an insulin-like growth factor I antisense in the

inferior olive of adult rats, a procedure which we previously

found to elicit a significant and reversible decrease of

insulin-like growth factor I levels in the contralateral

cerebellum. Ultrastructural analysis of the cerebellar cortex

of these animals showed a significant reduction in the size of

dendritic spines on Purkinje cells of antisense-treated rats

compared to controls. The decrease in spine size was linked to

a diminished numerical density of dendritic spines on Purkinje

cells, without affecting the numerical density of synapses in

the molecular layer of the cerebellum. This reduction was not

due to a change in the thickness of the molecular layer.

Climbing or parallel fiber terminals were also unaffected.

Taken together with previous findings, these results support a

role for insulin-like growth factor I produced in the inferior

olive in the maintenance of Purkinje cell synaptic plasticity..

0; 67763-96-6.

136. Nowak, A. J.; Marshall Goodell, B.; Kehoe, E. J.; Gormezano, I.

Elicitation, modification, and conditioning of the rabbit

nictitating membrane response by electrical stimulation in the

spinal trigeminal nucleus, inferior olive, interpositus nucleus,

and red nucleus. Behav-Neurosci. 1997 Oct; 111(5): 1041-55;

ISSN: 0735-7044.

UNITED-STATES. Elicitation of responses by electrical brain

stimulation (EBS) was related to the synaptic distance of the

target nucleus from the accessory abducens. Specifically,

responses to EBS in the spinal trigeminal nucleus (TRIG) and

red nucleus (RN) increased as a positive function of

stimulation parameters. Responding to EBS in the interpositus

nucleus (IP) was lower, and responding to EBS in the inferior

olive (IO) was negligible. EBS in the TRIG, IP, and RN nuclei

was then paired with a tone conditioned stimulus (CS). The CS

modified responses for EBS in RN and TRIG but not IP. CS-EBS

pairings yielded conditioned response (CR) acquisition, in

which Groups TRIG, IP, and RN reached asymptotes of 90%,

70%, and 43% CRs, respectively. Thus, contrary to previous

findings, EBS in the efferent pathway can support CR

acquisition. The results are discussed with respect to the role

of projections from the RN to the cerebellar cortex and the

TRIG nucleus.

137. Nusser, Z.; Sieghart, W.; Somogyi, P. Segregation of different

GABAA receptors to synaptic and extrasynaptic membranes of

cerebellar granule cells. J-Neurosci. 1998 Mar 1; 18(5): 1693-

703; ISSN: 0270-6474.

UNITED-STATES. Two types of GABAA receptor-mediated

inhibition (phasic and tonic) have been described in cerebellar

granule cells, although these cells receive GABAergic input

only from a single cell type, the Golgi cell. In adult rats,

granule cells express six GABAA receptor subunits abundantly

(alpha1, alpha6, beta2, beta3, gamma2, and delta), which are

coassembled into at least four to six distinct GABAA receptor

subtypes. We tested whether a differential distribution of

GABAA receptors on the surface of granule cells could play a

role in the different forms of inhibition, assuming that phasic

inhibition originates from the activation of synaptic

receptors, whereas tonic inhibition is provided mainly by

extrasynaptic receptors. The alpha1, alpha6, beta2/3, and

gamma2 subunits have been found by immunogold localizations

to be concentrated in GABAergic Golgi synapses and also are

present in the extrasynaptic membrane at a lower

concentration. In contrast, immunoparticles for the delta

subunit could not be detected in synaptic junctions, although

they were abundantly present in the extrasynaptic dendritic

and somatic membranes. Gold particles for the alpha6,

gamma2, and beta2/3, but not the alpha1 and delta, subunits

also were concentrated in some glutamatergic mossy fiber

synapses, where their colocalization with AMPA-type

glutamate receptors was demonstrated. The exclusive

extrasynaptic presence of the delta subunit-containing

receptors, together with their kinetic properties, suggests

that tonic inhibition could be mediated mainly by

extrasynaptic alpha6beta2/3delta receptors, whereas phasic

inhibition is attributable to the activation of synaptic

alpha1beta2/3gamma2, alpha6beta2/3gamma2, and

alpha1alpha6beta2/3gamma2 receptors.. 0.

138. Offermanns, S.; Hashimoto, K.; Watanabe, M.; Sun, W.; Kurihara, H.;

Thompson, R. F.; Inoue, Y.; Kano, M.; Simon, M. I. Impaired motor

coordination and persistent multiple climbing fiber

innervation of cerebellar Purkinje cells in mice lacking

Galphaq. Proc-Natl-Acad-Sci-U-S-A. 1997 Dec 9; 94(25):

14089-94; ISSN: 0027-8424.

UNITED-STATES. Mice lacking the alpha-subunit of the

heterotrimeric guanine nucleotide binding protein Gq (Galphaq)

are viable but suffer from ataxia with typical signs of motor

discoordination. The anatomy of the cerebellum is not overtly

disturbed, and excitatory synaptic transmission from parallel

fibers to cerebellar Purkinje cells (PCs) and from climbing

fibers (CFs) to PCs is functional. However, about 40% of adult

Galphaq mutant PCs remain multiply innervated by CFs because

of a defect in regression of supernumerary CFs in the third

postnatal week. Evidence is provided suggesting that Galphaq

is part of a signaling pathway that is involved in the

elimination of multiple CF innervation during this period.. 0.

139. O'Hearn, E.; Molliver, M. E. The olivocerebellar projection mediates

ibogaine-induced degeneration of Purkinje cells: a model of

indirect, trans-synaptic excitotoxicity. J-Neurosci. 1997 Nov

15; 17(22): 8828-41; ISSN: 0270-6474.

UNITED-STATES. Ibogaine, an indole alkaloid that causes

hallucinations, tremor, and ataxia, produces cerebellar

neurotoxicity in rats, manifested by degeneration of Purkinje

cells aligned in narrow parasagittal bands that are

coextensive with activated glial cells. Harmaline, a closely

related alkaloid that excites inferior olivary neurons, causes

the same pattern of Purkinje cell degeneration, providing a

clue to the mechanism of toxicity. We have proposed that

ibogaine, like harmaline, excites neurons in the inferior olive,

leading to sustained release of glutamate at climbing fiber

synapses on Purkinje cells. The objective of this study was to

test the hypothesis that increased climbing fiber activity

induced by ibogaine mediates excitotoxic Purkinje cell

degeneration. The inferior olive was pharmacologically ablated

in rats by a neurotoxic drug regimen using 3-acetylpyridine,

and cerebellar damage attributed to subsequent administration

of ibogaine was analyzed using immunocytochemical markers

for neurons and glial cells. The results show that ibogaine

administered after inferior olive ablation produced little or no

Purkinje cell degeneration or glial activation. That a lesion of

the inferior olive almost completely prevents the

neurotoxicity demonstrates that ibogaine is not directly toxic

to Purkinje cells, but that the toxicity is indirect and

dependent on integrity of the olivocerebellar projection. We

postulate that ibogaine-induced activation of inferior olivary

neurons leads to release of glutamate simultaneously at

hundreds of climbing fiber terminals distributed widely over

the surface of each Purkinje cell. The unique circuitry of the

olivocerebellar projection provides this system with maximum

synaptic security, a feature that confers on Purkinje cells a

high degree of vulnerability to excitotoxic injury.. 0; 0; 0;

304-21-2; 462-08-8; 83-74-9; 98-92-0.

140. Ohyu, J.; Yamanouchi, H.; Takashima, S. Immunohistochemical

study of microtubule-associated protein 5 (MAP5) expression

in the developing human brain. Brain-Dev. 1997 Dec; 19(8):

541-6; ISSN: 0387-7604.

NETHERLANDS. The expression of microtubule-associated

protein 5 (MAP5) in the developing human brain was studied by

means of an immunohistochemical method. In the cerebellum,

MAP5 immunoreactivity appeared in the molecular layer and

subcortical white matter from the early fetal age of 13

gestational weeks (GW), and temporally increased in the outer

halves of the molecular layer and subcortical white matter at

36 GW to 2 months of age and 20 to 22 GW, respectively. In the

cerebrum, it already appeared in the molecular layer and

subcortical white matter from 13 GW, and was marked at 20

to 26 GW and 24 to 32 GW, respectively. Cortical pyramidal

neurons gradually became immunoreactive from 28 GW to

adolescence. Ependymal cilia were markedly positive in

ventricular wall in all ages. In Western blot analyses, MAP5

showed two separate molecular weight bands. In the fetal

period 320 kDa protein was prominent, but 300 kDa protein

could be detected only at 11 years of age. Thus MAP5 was

markedly expressed in growing axon in the fetal period and

may be essential for the elongation and maturation as well as

the function maintenance of axons and dendrites in developing

human brain.. 0; 0; 0.

141. Ojemann, J. G.; Neil, J. M.; MacLeod, A. M.; Silbergeld, D. L.; Dacey,

RG Jr; Petersen, S. E.; Raichle, M. E. Increased functional

vascular response in the region of a glioma. J-Cereb-Blood-

Flow-Metab. 1998 Feb; 18(2): 148-53; ISSN: 0271-678X.

UNITED-STATES. Functional imaging of a language task using

positron emission tomography was performed as part of the

preoperative assessment of a patient with a left

supplementary motor area (SMA) tumor. Positron emission

tomography scans were obtained during language tasks (verb

generation and word reading of visually presented nouns) that

normally lead to increased blood flow in the SMA relative to a

control condition (visual fixation). In the patient, the normal

SMA response was an order of magnitude larger in the region

of the tumor. Other regions, such as left inferior frontal

cortex and right cerebellum, showed equivalent activation in

the patient and normal subjects. Histopathologic study

revealed an anaplastic astrocytoma. Thus, this exaggerated

vascular response to local neuronal activation occurred in the

setting of a proliferation of glial cells. This is consistent

with models of coupling of regional CBF and neuronal activity

that implicate glia as the mediator between neurons and

vasculature. The concept that tumoral disruption of normal

vascular responses could, in some cases, potentially enhance

rather than dampen the response is proposed.

142. Ono, K.; Shokunbi, T.; Nagata, I.; Tokunaga, A.; Yasui, Y.; Nakatsuji,

N. Filopodia and growth cones in the vertically migrating

granule cells of the postnatal mouse cerebellum. Exp-Brain-

Res. 1997 Oct; 117(1): 17-29; ISSN: 0014-4819.

GERMANY. The details of the morphology of vertically

migrating granule cells were examined semiquantitatively in

the postnatal mouse cerebellum by a Golgi method, with

special reference to the growth cone-related structures such

as filopodia and lamellipodia. The first sign of inward

migration was extension of short, vertical filopodium-like

processes from the sides of the perikarya of tangentially

oriented granule cells, followed by a change of orientation of

cell bodies to the vertical axis showing a T-shaped

morphology. The T-shaped migratory cells formed sprouted

filopodia (side spikes) from their vertical leading processes

and perikarya at right angles to the vertical axis. More than

three-quarters of the migratory cells extended the side spikes.

The presence of such side spikes was confirmed with laser

scanning confocal microscopy of granule cells labeled with

1,1', dioctadecyl-3,3,3',3-tetramethylindocarbocyanine

perchlorate and also with transmission electron microscopy

(TEM). In addition, about one-fourth of migratory cells

extended lamellipodia of web-like forms along the stem or at

the tip of the leading process, some of which showed a typical

growth cone. Several morphological variations of vertical

granule cells were also observed. Furthermore, TEM

observation confirmed that side spikes from migratory cells

made direct contact with parallel fibers. The present results

suggest that, during vertical migration, growth cone-related

structures of the leading processes of granule cells adhere to

and probably recognize tangentially oriented parallel fibers.

Therefore, the mechanisms of the vertical guidance and

migration of granule cells in the cerebellar cortex seem to be

multiple, involving not only parallel contact guidance by the

Bergmann glia fibers but also perpendicular contact guidance

by the parallel fibers. These parallel and perpendicular

geometric cues surrounding the granule cells seem to have

produced the varying morphology of vertically migrating

granule cells.. 0; 0; 40957-95-7.

143. Ouyang, Y.; Martone, M. E.; Deerinck, T. J.; Airey, J. A.; Sutko, J. L.;

Ellisman, M. H. Differential distribution and subcellular

localization of ryanodine receptor isoforms in the chicken

cerebellum during development. Brain-Res. 1997 Nov 14;

775(1-2): 52-62; ISSN: 0006-8993.

NETHERLANDS. The distribution of ryanodine receptor (RyR)

isoforms was examined using isoform-specific monoclonal

antibodies in the developing chicken brain, from E18 through

adulthood, using light and electron microscopic

immunocytochemistry. Monoclonal antibody 110F is specific

for the alpha-skeletal muscle form of RyR, while monoclonal

antibody 110E recognizes both the beta-skeletal muscle and

cardiac isoforms, but does not distinguish between the two.

Significant differences in the distribution of the alpha- and

beta/cardiac forms were observed. Labeling for the alpha-form

was restricted to cerebellar Purkinje neurons while the

beta/cardiac form was observed in neurons throughout the

brain. A major finding was the presence of labeling for the

beta/cardiac in presynaptic terminals of the parallel fibers in

the molecular layer and the mossy fiber terminals in the

granular layer glomeruli in late development and during

adulthood. Labeling for the beta/cardiac, but not the alpha-

form, underwent a major redistribution in the cerebellum

during the course of development. At 1 day of age,

beta/cardiac labeling was present mainly in Purkinje neurons.

From 1 day to 4 weeks, immunolabeling for the beta/cardiac

form gradually disappeared from Purkinje neurons, but

increased in granule cells. Within the molecular layer, the

labeling pattern changed from being primarily within Purkinje

dendrites to a more diffuse pattern. Electron microscopic

examination of the cerebellar molecular layer of 2-week-old

chicks revealed that beta/cardiac-labeling was mainly present

in the axons and presynaptic processes of the parallel fibers.

No developmental changes were observed in other brain

regions. This study represents the first demonstration of

ryanodine receptor immunoreactivity in presynaptic boutons

and suggests that the ryanodine receptor may modulate

neurotransmitter release through local regulation of

intracellular calcium in the parallel fiber synapse.. 0; 0.

144. Pascual, R.; Hervias, M. C.; Toha, M. E.; Valero, A.; Figueroa, H. R.

Purkinje cell impairment induced by early movement

restriction. Biol-Neonate. 1998; 73(1): 47-51; ISSN: 0006-

3126.

SWITZERLAND. In the present work the effects of movement

restriction imposed during the early postweaning period on

both Purkinje cell dendritic development and exploratory

behavior were analyzed. Male and female Sprague-Dawley

albino rats were reared either in isolated-restricted or

social-standard environments from postnatal day 18 to 30. On

the 31st postnatal day, all rats were behaviorally evaluated by

the open-field test and then sacrificed under deep ether

anesthesia. Vermian cerebellar sections were later stained

with the Golgi-Cox-Sholl method and the Purkinje cell

dendritic morphology was quantified under light microscopy.

The results indicate that early somatomotor restriction

severely impairs both exploratory behavior and Purkinje cell

dendritic growth.

145. Paterson, I. A.; Zhang, D.; Warrington, R. C.; Boulton, A. A. R-

deprenyl and R-2-heptyl-N-methylpropargylamine prevent

apoptosis in cerebellar granule neurons induced by cytosine

arabinoside but not low extracellular potassium. J-Neurochem.

1998 Feb; 70(2): 515-23; ISSN: 0022-3042.

UNITED-STATES. R-Deprenyl and R-2-heptyl-N-

methylpropargylamine (R-2-HMP) are compounds that have

been shown to reduce neuronal death in various in vitro and in

vivo models involving apoptosis but do not always prevent

apoptosis. In the present study we have examined the effects

of these compounds and their S enantiomers on cytosine

arabinoside (ara C)-induced apoptosis and low K+-induced

apoptosis in cerebellar granule cells in primary culture. It was

found that R-deprenyl and R-2-HMP could prevent ara C-

induced apoptosis with an EC50 around 10(-9) M but could not

prevent low K+-induced apoptosis. S-Deprenyl and S-2-HMP did

not prevent apoptosis under any conditions but were found to

antagonize the antiapoptotic actions of R-deprenyl and R-2-

HMP. Using the fluorescent mitochondrial dye

chloromethyltetramethylrhodamine methyl ester it was found

that there was a loss of mitochondrial function in cerebellar

granule cells exposed to ara C but not low K + medium. R-

Deprenyl and R-2-HMP prevented the ara C-induced loss of

mitochondrial function. It is concluded that R-deprenyl and R-

2-HMP prevent apoptosis of cerebellar granule cells by a

mechanism that is independent of monoamine oxidase

inhibition and that they act on the same site to prevent

specifically apoptosis involving a loss of mitochondrial

membrane potential, possibly p53-dependent apoptosis.. 0;

143347-04-0; 14611-51-9; 147-94-4; 7440-09-7.

146. Pellerin, J. P.; Lamarre, Y. Local field potential oscillations in

primate cerebellar cortex during voluntary movement. J-

Neurophysiol. 1997 Dec; 78(6): 3502-7; ISSN: 0022-3077.

UNITED-STATES. Sustained oscillations of 13-18 Hz were

observed in local field potentials (LFPs) in the cerebellar

cortex of a behaving monkey. These oscillations, which

appeared to be generated in the granular cell layer, were

particularly prominent in the paramedian lobule. The

oscillatory activity decreased during drowsiness or extreme

arousal and occurred most often when the animal was

immobile but alert. In a task requiring the animal to move the

arm approximately 1 s after an auditory cue, the oscillations

stopped some 150-200 ms after the cue, resumed 200-300 ms

later, and stopped again 50-100 ms before movement onset.

This modulation pattern was observed with consistency only

when the animal responded reliably to the auditory cue. The

results suggest that the cerebellum could be involved in some

higher level of integration particularly during complex

sensorimotor behavior.

147. Percheron, G. The motor thalamus [letter]. J-Neurosurg. 1997 Dec;

87(6): 981-2; ISSN: 0022-3085.

UNITED-STATES.

148. Pisciotta, M.; Coronas, F. I.; Possani, L. D.; Prestipino, G. The

Androctonus australis garzoni scorpion venom contains toxins

that selectively affect voltage-dependent K(+)-channels in

cerebellum granular cells. Eur-Biophys-J. 1998; 27(1): 69-73;

ISSN: 0175-7571.

GERMANY. A purified peptide from Androctonus australis

Garzoni venom (AaG) affects selectively a K(+)-current

recorded from cerebellum granular cells. This current is

characterized by fast activating and inactivating kinetics

similar to an IA-type current. Addition of 2 microM peptide

Aa1 (from Androctonus australis, toxin 1) to the external side

of the channel suppressed completely and in a selective

manner the IA-type current, with an IC50 value of 130 nM,

whereas in the same conditions, the other potassium current,

identified as delayed rectifier (Id), was not affected.

Additionally, we show that another partially purified peptide

(III-12) from the same venom was able to block reversibly

both K(+)-currents.. 0; 0; 0; 7440-09-7.

149. Plotkin, M. D.; Snyder, E. Y.; Hebert, S. C.; Delpire, E. Expression of

the Na-K-2Cl cotransporter is developmentally regulated in

postnatal rat brains: a possible mechanism underlying GABA's

excitatory role in immature brain. J-Neurobiol. 1997 Nov 20;

33(6): 781-95; ISSN: 0022-3034.

UNITED-STATES. An inhibitory neurotransmitter in mature

brain, gamma-aminobutyric acid (GABA) also appears to be

excitatory early in development. The mechanisms underlying

this shift are not well understood. In vitro studies have

suggested that Na-K-Cl cotransport may have a role in

modulating immature neuronal and oligodendrocyte responses

to the neurotransmitter GABA. An in vivo developmental study

would test this view. Therefore, we examined the expression

of the BSC2 isoform of the Na-K-2Cl cotransporter in the

postnatal developing rat brain. A comparison of sections from

developing rat brains by in situ hybridization revealed a well-

delineated temporal and spatial pattern of first increasing and

then diminishing cotransporter expression. Na-K-2Cl mRNA

expression in the cerebral cortex and hippocampus was highest

in the first week of postnatal life and then diminished from

postnatal day (PND) 14 to adult. Cotransporter signal in white-

matter tracts of the cerebrum, cerebellum, peaked at PND 14.

Expression was detected in cerebellar progenitor cells of the

external granular layer, in internal granular layer cells at

least as early as PND 7, and in Purkinje cells beginning at PND

14. Double-labeling immunofluorescence of brain sections

with anti-BSC2 antibody and cell type-specific antibodies

confirmed expression of the cotransporter gene product in

neurons and oligodendrocytes in the white matter in a pattern

similar to that determined by in situ hybridization. The

temporal pattern of expression of the Na-K-2Cl cotransporter

in the postnatal rat brain supports the hypothesis that the

cotransporter is the mechanism of intracellular Cl-

accumulation in immature neurons and oligodendrocytes.. 0; 0;

0; 56-12-2.

150. Podda, M. V.; Deriu, F.; Solinas, A.; Demontis, M. P.; Varoni, M. V.;

Spissu, A.; Anania, V.; Tolu, E. Effect of atrazine

administration on spontaneous and evoked cerebellar activity

in the rat. Pharmacol-Res. 1997 Sep; 36(3): 199-202; ISSN:

1043-6618.

ENGLAND. The effect of atrazine oral administration on

cerebellar forelimb projection area was studied in rats in

vivo. Rats acutely treated with atrazine (100 mg kg-1, BW)

showed a significant decrease in spontaneous Purkinje cell

firing rate. Atrazine also decreased the cerebellar potentials

evoked by electrical stimulation of the ipsilateral radial

nerve, affecting mostly the response to climbing fiber input.

These results demonstrate that atrazine exerts a toxic action

on central nervous system. The effects on the cerebellar

somatosensory cortex could be responsible for motor disorders

frequently observed in animals intoxicated with atrazine.

Copyright 1997 The Italian Pharmacological Society.. 0; 1912-

24-9.

151. Ponomareva, E. N.; Astapenko, A. V.; Likhachev, S. A.; Ovsiankina, G.

I.; Pashko, G. V.; Antonenko, A. I. [The cerebellar cortical

atrophy syndrome]. Sindrom kortikal'noi mozzhechkovoi

atrofii. Zh-Nevrol-Psikhiatr-Im-S-S-Korsakova. 1997; 97(9):

14-9.

RUSSIA. The results of the observation of 44 patients with

cerebellar syndrome of different etiology are presented.

Together with careful study of anamnestic and clinical data

some additional examinations were performed: senso- and

pallesthesiometry, thermovisional investigation,

vestibulometry, electroencephalo-, electromyography,

computer tomography. The study allowed to reveal both the

cause of the disease and to refer etiologically late cerebellar

cortical ataxia to alcohol factor. On the basis of the

comparison of clinical neurological data with paraclinical

observation differential diagnostic criteria were defined for

Marie-Foix-Alajouanine's late cortical cerebellar atrophy in

alcoholism, in the cases of the hereditary predisposition as

well as of unclear genesis, in Holmes olivocerebellar atrophy,

in Menzel, Hunt and Dejerine-Thomas olivopontocerebellar

degeneration.

152. Pouzat, C.; Hestrin, S. Developmental regulation of

basket/stellate cell-->Purkinje cell synapses in the

cerebellum. J-Neurosci. 1997 Dec 1; 17(23): 9104-12; ISSN:

0270-6474.

UNITED-STATES. We used paired recordings to study the

development of synaptic transmission between inhibitory

interneurons of the molecular layer and Purkinje cells in the

cerebellar cortex of the rat. The electrophysiological data

were combined with a morphological study of the recorded

cells using biocytin or Lucifer yellow staining. Thirty-one

interneuron-Purkinje cell pairs were obtained, and 11 of them

were recovered morphologically. The age of the rats ranged

from 11 to 31 d after birth. During this period synaptic

maturation resulted in an 11-fold decrease in the average

current evoked in a Purkinje cell by a spike in a presynaptic

interneuron. Unitary IPSCs in younger animals exhibited

paired-pulse depression, whereas paired-pulse facilitation

was found in more mature animals. These data suggest that

reduction in transmitter release probability contributed to the

developmental decrease of unitary IPSCs. However, additional

mechanisms at both presynaptic and postsynaptic loci should

also be considered. The decrease of the average synaptic

current evoked in a Purkinje cell by an action potential in a

single interneuron suggests that as development proceeds

interneuron activities must be coordinated to inhibit

efficiently Purkinje cells.

153. Proust, F.; Callonec, F.; Bellow, F.; Laquerriere, A.; Hannequin, D.;

Freger, P. Tentorial edge traumatic aneurysm of the superior

cerebellar artery. Case report. J-Neurosurg. 1997 Dec; 87(6):

950-4; ISSN: 0022-3085.

UNITED-STATES. The authors report an unusual case of a

traumatic aneurysm of the right superior cerebellar artery

(SCA). A 22-year-old woman presented with continuous

headaches that appeared 15 days after she experienced closed

head trauma as a result of a cycling accident. Computerized

tomography scanning performed 3 months later showed a

nodular lesion on the free edge of the tentorium, which

mimicked a meningioma. The aneurysm was identified on

magnetic resonance angiography, which showed the SCA as the

parent vessel. The parent vessel was trapped, and the

aneurysm sac was excised via right temporal craniotomy.

Pathological examination of the sac revealed a false aneurysm.

The patient's outcome was excellent. The pathophysiology of

traumatic aneurysm at such a location suggests that surgery

may be the treatment of choice.

154. Przyborski, S. A.; Knowles, B. B.; Ackerman, S. L. Embryonic

phenotype of Unc5h3 mutant mice suggests chemorepulsion

during the formation of the rostral cerebellar boundary.

Development. 1998 Jan; 125(1): 41-50; ISSN: 0950-1991.

ENGLAND. Mutation of the Unc5h3 (formally known as rcm)

gene has important consequences on neuronal migration during

cerebellar development. Unc5h3 transcripts are expressed

early (embryonic day 8.5) in the hindbrain region and later in

the cerebellar primordia. In Unc5h3 mutant embryos, both the

development and initial migration of Purkinje cell progenitors

occur as in wild-type controls. The rhombic lip, from which

granule cell precursors arise, also appears to form normally in

mutants. However, at E13.5, an abnormal subpopulation of

granule cell and Purkinje cell precursors becomes detectable

in rostral areas of the Unc5h3 mutant brain stem. These

ectopic cerebellar cells increase in number and continue

moving in a rostral direction throughout the remainder of

embryogenesis and early stages of postnatal development

invading the lateral regions of the pontine area and eventually

the inferior colliculus. Cell proliferation markers demonstrate

the mitotic nature of these subpial ectopic granule neurons

indicating the displacement of the rostral external germinal

layer in mutant animals. Our data suggest that establishment

of the rostral cerebellar boundary may rely on chemorepulsive

signaling events that require UNC5H3 expressed by cerebellar

neurons and extracellular ligands that are functionally related

to the UNC5H3-binding, guidance molecule netrin1. Although

the phenotype resulting from the Unc5h3 mutation is

apparently limited to the formation of the cerebellum,

additional sites of Unc5h3 expression are also found during

development suggesting the compensatory function of other

genes.. 0; 0; 0; 158651-98-0.

155. Puzdrowski, R. L. Anti-Zebrin II immunopositivity in the

cerebellum and octavolateral nuclei in two species of

stingrays. Brain-Behav-Evol. 1997; 50(6): 358-68; ISSN: 0006-

8977.

SWITZERLAND. Anti-Zebrin II is an antibody directed against a

36kDa aldolase epitope expressed by Purkinje cells. Two

patterns of Zebrin II immunolabeling have been described in

the cerebellar corpus. In mammalian cerebella, the anti-Zebrin

II labels longitudinal zones of Purkinje cells, whereas in

teleosts, all Purkinje cells of the cerebellar corpus are Zebrin

II immunopositive. An outgroup analysis is required to

determine which of these distribution patterns represents the

primitive condition for jawed vertebrates. The sister group of

the Osteichthyans (rayfinned fishes, amphibians, and

amniotes) is the Chondrichthyans (sharks, skates, and rays). In

the present study the distribution of Zebrin II

immunopositivity was examined in the Atlantic stingray and

the Southern stingray. Western-blot analysis demonstrates

that the Zebrin II antibody recognizes an antigen of the same

molecular weight in stingrays, teleosts, and mammals. In

stingrays, anti-Zebrin II immunohistochemistry reveals a

staining pattern in which all Purkinje cells are

immunopositive, no banding pattern or zonal compartmentation

is observed. Purkinje cell axon projections to the cerebellar

nucleus and the octaval nuclei are also revealed. Within the

octaval nuclei, immunopositive Purkinje cell axon terminals

and boutons en passant were found in the anterior, descending,

and posterior nuclei. These immunopositive profiles are found

throughout these nuclei, but they are most dense in the lateral

and ventral portions. Except for the dorsolateralmost portion,

the magnocellular nucleus does not appear to receive Purkinje

cell inputs. Based on these results it is concluded that the

Zebrin II distribution pattern in which all Purkinje cells of the

cerebellar corpus are immunopositive is the primitive

condition for jawed vertebrates.. 0; 0.

156. Raabe, T. D.; Suy, S.; Welcher, A.; DeVries, G. H. Effect of neu

differentiation factor isoforms on neonatal oligodendrocyte

function. J-Neurosci-Res. 1997 Dec 1; 50(5): 755-68; ISSN:

0360-4012.

UNITED-STATES. Previous studies have suggested that neu

differentiation factor (NDF), a member of the neuregulin (NRG)

family of growth factors, may regulate the development of

PNS and CNS glial cells. There is limited information

concerning the potential role of NDF on the development of

neonatal (immature) oligodendrocytes (OLG) into adult OLG. We

now report the effect of the two major isoform families of

NDF (NDF alpha and NDF beta) on the development of cultured

rat neonatal OLG. Immunocytochemical and western blot

analyses of neonatal OLG using anti-erb-B antibodies revealed

that these immature OLG express all four members of NRG

(erb-B) receptors. Treatment of neonatal OLG with varying

concentrations of either NDF alpha or NDF beta did not have a

mitogenic effect on cultured neonatal OLG. Pretreatment of

immature OLG with either of the NDF isoforms also did not

influence the subsequent mitogenicity of other known OLG

mitogens. However, treatment of neonatal OLG with either

isoform of NDF influenced the survival of these cells by

protecting the cells from apoptosis. Additionally, treatment of

neonatal OLG with either NDF alpha or NDF beta resulted in

more extensive process formation compared to control, non-

treated OLG.. 0; 0; 0; 0; 0; 0.

157. Ramaekers, V. T.; Heimann, G.; Reul, J.; Thron, A.; Jaeken, J.

Genetic disorders and cerebellar structural abnormalities in

childhood. Brain. 1997 Oct; 120( Pt 10): 1739-51; ISSN: 0006-

8950.

ENGLAND. Amongst 78 patients with either unilateral or

bilateral (ponto-) cerebellar hypoplasia, atrophy or lesions on

neuro-imaging (CT and/or MRI), 16 showed unilateral

hypoplasia or lesions, 15 vermis defects, nine pontocerebellar

hypoplasia, 10 non-progressive conditions with bilateral

cerebellar hemisphere hypoplasia or lesions and 28

progressive cerebellar atrophy. Known genetic conditions did

not occur with unilateral cerebellar involvement, whereas a

high incidence of mostly autosomal recessively inherited

diseases could be diagnosed in more than half of the patients

with either pontocerebellar hypoplasia or progressive

bilateral cerebellar atrophy. A minority of patients with

vermis defects or non-progressive cerebellar hypoplasia

suffered from genetic conditions. An overview of the

literature is presented describing genetic and non-genetic

syndromes, or metabolic disorders associated with cerebellar

structural abnormalities. From these data, new proposals for

improved diagnostic investigations will be presented.

158. Rathelot, J. A.; Padel, Y. Ascending spinal influences on

rubrospinal cells in the cat. Exp-Brain-Res. 1997 Sep; 116(2):

326-40; ISSN: 0014-4819.

GERMANY. Somaesthetic input to rubrospinal cells, bypassing

the cerebellum and cerebral cortex, has been demonstrated in

the cat. The detailed organization of this somatic afferent

system was studied using electrophysiological methods on

multiple-lesion, chloralose-anaesthetized preparations.

Stimulation of the dorsal column (DC) at upper cervical cord

segments induced significant responses in magnocellular red

nucleus (RNm) cells in cats without a cerebellum and with

ablation of the frontal cortex. As classic descriptions state

that primary afferent fibres have ascending and descending

branches in the DC, with many collaterals arborizing in the

grey matter at the segmental level of the cord, this procedure

is equivalent to stimulating the somatic fibres coming from a

large portion of the body, leading to the simultaneous

activation of most ascending spinal pathways. To show that

the pathway responsible for the rubral responses ascends in

the ventral spinal cord, and that the synaptic relays are

located at the segmental level, the stimulation was applied to

the DC, caudally to the sectioned dorsal spinal half. Various

tests confirmed that the activation was conducted to rubral

cells through antidromically activated primary afferents.

Their multiple collaterals relay the messages to cells located

caudal to the spinal lesion, with fibres ascending in the

ventral cord. Any relay of the somatic rubral responses in the

DC's nuclei was excluded. When the DC was sectioned and its

rostral end was dissected free and lifted onto two hook

electrodes for stimulation, no response was obtained in the

rubral cells. This dissection indeed sectioned all DC fibre

collaterals entering the grey matter, thus excluding the

possibility of segmental relay. Single shocks applied to the

ventral quadrant of the cord or in the medial lemniscus (LM) in

the medulla oblongata induced monosynaptic excitatory post-

synaptic potentials (EPSPs) in most rubrospinal cells. The

spinal EPSPs could be collided by stimulation in the LM, thus

demonstrating the existence of direct connections from the

cord to the RNm. This somaesthetic pathway to the RNm could

be involved in on-line correction of movements and in learning

new motor strategies.

159. Raz, N.; Dupuis, J. H.; Briggs, S. D.; McGavran, C.; Acker, J. D.

Differential effects of age and sex on the cerebellar

hemispheres and the vermis: a prospective MR study. AJNR-

Am-J-Neuroradiol. 1998 Jan; 19(1): 65-71; ISSN: 0195-6108.

UNITED-STATES. PURPOSE: The purpose of this study was to

determine the effects of age and sex on the size of the

cerebellar hemispheres, the cerebellar vermis, and the pons in

healthy adults. METHODS: We estimated the volumes of the

cerebellar hemispheres (excluding the vermis and the

peduncles), the cross-sectional area of the vermis, and the

cross-sectional area of the ventral pons from MR images

obtained in 146 healthy volunteers, 18 to 77 years old.

RESULTS: We found a mild but significant age-related

reduction in the volume of the cerebellar hemispheres and in

the total area of the cerebellar vermis; however, the analysis

of age trends in the vermian lobules revealed differential age-

related declines. The areas of lobules VI and VII and of the

posterior vermian lobules (VIII-X) declined significantly with

age, whereas the anterior vermis (I-V) showed no significant

age-related shrinkage. The volume of the cerebellar

hemispheres (especially the right) and the area of the anterior

vermis were greater in men, even after adjustment for height.

Neither age nor sex affected the area of the ventral pons.

CONCLUSIONS: Normal aging of the cerebellum is associated

with selective regional shrinkage. The cerebellar hemispheres

and the area of the anterior vermis may be larger in men than

in women regardless of differences in body size.

160. Redekop, G. J.; Durity, F. A.; Woodhurst, W. B. Management-related

morbidity in unselected aneurysms of the upper basilar artery.

J-Neurosurg. 1997 Dec; 87(6): 836-42; ISSN: 0022-3085.

UNITED-STATES. A series of 49 consecutively treated patients

with 52 aneurysms of the upper basilar artery (BA) is

presented. Thirty-nine aneurysms arose at the BA bifurcation,

11 at the origin of the superior cerebellar artery (SCA), and

two from the upper BA trunk just below the SCA. The patient

population consisted of 36 women and 13 men, with a mean

age of 50 years (range 23-74 years). Of the 35 patients

presenting with subarachnoid hemorrhage, 10 were Grade I, 10

were Grade II, 11 were Grade III, and four were Grade IV

according to the Hunt and Hess scale. Treatment consisted of

aneurysm neck clipping in 28, proximal occlusion of the BA in

three, and endovascular therapy with coils in four patients.

The remaining 14 patients with unruptured aneurysms

underwent direct neck clipping. Postoperatively, 38 patients

developed diplopia in at least one direction of gaze but this

had resolved in 31 of them at the last follow-up evaluation.

There were four deaths (8.2%): two as a result of rebleeding

following coil compaction at 8 days and 9 months

posttreatment, respectively; one as a result of vasospasm; and

one as a result of brainstem infarction after proximal

occlusion of the BA in a giant bifurcation aneurysm. Of the

surviving patients, 33 (67.3%) made an excellent recovery,

seven (14.3%) made a good recovery, and five (10.2%) were in

poor condition at the last follow-up review. Direct

microsurgical clipping of most aneurysms of the BA apex

region can be performed with acceptable rates of morbidity.

These data from an unselected series of patients in a general

hospital provide a basis for comparison with developing

alternative techniques.

161. Reichenbach, A.; Siegel, A.; Senitz, D.; Smith, TG Jr. A comparative

fractal analysis of various mammalian astroglial cell types.

Neuroimage. 1992 Aug; 1(1): 69-77; ISSN: 1053-8119.

UNITED-STATES. Camera-lucida drawings of Golgi-

impregnated astroglial cells and their processes are described

by the fractal dimension of their borders, which is an

objective, quantitative measure of morphological complexity.

Protoplasmic astrocytes from human neocortex have fractal

dimensions (D) that are larger than those of fibrous astrocytes

from the cat optic nerve. Marginal astrocytes from monkey

cerebropontile angle have two kinds of processes: (1) short,

thick processes with endfeet abutting the pial surface, with

relatively high D's, and (2) very long, thin processes extending

into the neuronal tissue, with very low D's. These data indicate

that short astrocytic processes may have a complex surface

(and have a high D), whereas long processes are rather smooth

(and have a low D). A comparison between transmission

electron microscopy morphometry and measures of D at the

light microscopic level, performed on different parts of rabbit

retinal Muller glial cells, suggests that D is strongly

correlated to the surface-to-volume ratio which, in part,

determines the length constant of a cable for core-

conductance of currents. We provide data supporting the

hypothesis that astroglial cell geometry is adjusted to allow

for sufficient spatial buffering K+ currents, even through very

long processes.

162. Romero Lopez, J.; Moreno Carretero, M. J.; Escriche Jaime, D.;

Corredera Garcia, E.; Navarro Fernandez, Balbuena C. [The

association of Marchiafava-Bignami disease, cerebral pellagra

and cerebellar degeneration in an alcoholic patient].

Asociacion de enfermedad de Marchiafava-Bignami, pelagra

cerebral y degeneracion cerebelosa en un paciente alcoholico.

Rev-Neurol. 1997 Oct; 25(146): 1577-8; ISSN: 0210-0010.

SPAIN. INTRODUCTION: Marchiafava-Bignami disease, cerebral

pellagra and alcoholic cerebellar degeneration are a group of

diseases included in the alcoholic encephalopathies, although

they may also be caused by metabolic or nutritional disorders.

The isolated appearance of these diseases usually permits

diagnosis during the life of the patient, based on the neuro-

radiological findings. However, their combination leads to

complex form, with variable neurological expression, which

means that precise diagnosis may often be post mortem.

CLINICAL CASE: We present a malnourished alcoholic patient

with neurological features compatible with alcoholic

encephalopathy. The post mortem findings showed lesions

typical of alcoholic cerebellar degeneration, cerebral pellagra

and Marchiafava-Bignami disease.

163. Ross, C. A. Intranuclear neuronal inclusions: a common pathogenic

mechanism for glutamine-repeat neurodegenerative diseases?

Neuron. 1997 Dec; 19(6): 1147-50; ISSN: 0896-6273.

UNITED-STATES. 0; 0; 0; 0; 26700-71-0.

164. Ryu, H.; Yamamoto, S.; Sugiyama, K.; Uemura, K.; Miyamoto, T.

Hemifacial spasm caused by vascular compression of the

distal portion of the facial nerve. Report of seven cases. J-

Neurosurg. 1998 Mar; 88(3): 605-9; ISSN: 0022-3085.

UNITED-STATES. It is generally accepted that hemifacial

spasm (HFS) and trigeminal neuralgia are caused by

compression of the facial nerve (seventh cranial nerve) or the

trigeminal nerve (fifth cranial nerve) at the nerve's root exit

(or entry) zone (REZ); thus, neurosurgeons generally perform

neurovascular decompression at the REZ. Neurosurgeons tend to

ignore vascular compression at distal portions of the seventh

cranial nerve, even when found incidentally while performing

neurovascular decompression at the REZ of that nerve, because

compression of distal portions of the seventh cranial nerve

has not been regarded as a cause of HFS. Recently the authors

treated seven cases of HFS in which compression of the distal

portion of the seventh cranial nerve produced symptoms. The

anterior inferior cerebellar artery (AICA) was the offending

vessel in five of these cases. Great care must be taken not to

stretch the internal auditory arteries during manipulation of

the AICA because these small arteries are quite vulnerable to

surgical manipulation and the patient may experience hearing

loss postoperatively. It must be kept in mind that compression

of distal portions of the seventh cranial nerve may be

responsible for HFS in cases in which neurovascular

compression at the REZ is not confirmed intraoperatively and

in cases in which neurovascular decompression at the nerve's

REZ does not cure HFS. Surgical procedures for decompression

of the distal portion of the seventh cranial nerve as well as

decompression at the REZ should be performed when a deep

vascular groove is noticed at the distal site of compression of

the nerve.. 0; 0; 0; 0; 76900-80-6.

165. Sakashita, Y.; Kanai, M.; Sugimoto, T.; Taki, S.; Takamori, M.

Changes in cerebral blood flow and vasoreactivity in response

to acetazolamide in patients with transient global amnesia. J-

Neurol-Neurosurg-Psychiatry. 1997 Nov; 63(5): 605-10; ISSN:

0022-3050.

ENGLAND. OBJECTIVE: Previous reports about changes in

cerebral blood flow (CBF) in transient global amnesia

disclosed decreased flow in some parts of the brain. However,

CBF analyses in most reports were qualitative but not

quantitative. The purpose of this study was to determine

changes in CBF in transient global amnesia. METHODS: The CBF

was measured and the vasoreactive response to acetazolamide

was evaluated in six patients with transient global amnesia

using technetium-99m hexamethylpropylene amine oxime

single-photon emission computed tomography (SPECT). The CBF

was measured during an attack in two patients and soon after

an attack in the other four. About one month later, CBF was re-

evaluated in each patient. RESULTS: Two patients examined

during an attack and one patient examined five hours after an

attack had increased blood flow in the occipital cortex and

cerebellum. Three patients examined at six to 10 hours after

an attack had decreased blood flow in the thalamus,

cerebellum, or putamen. These abnormalities of blood flow

almost disappeared in all patients one month after onset. The

vasodilatory response to acetazolamide, which was evaluated

initially using SPECT, was poor in areas of increased blood

flow. By the second evaluation of CBF with acetazolamide, the

vasodilatory response had returned to normal. CONCLUSIONS: In

a patient with transient global amnesia, CBF increased in the

vertebrobasilar territory during the attack and decreased

afterwards. The vasodilatory response to acetazolamide may

be impaired in the parts of the brain with increased blood

flow. It is suggested that transient global amnesia is distinct

from migraine but may share the same underlying mechanism..

0; 0; 59-66-5.

166. Sapp, D. W.; Yeh, H. H. Ethanol-GABAA receptor interactions: a

comparison between cell lines and cerebellar Purkinje cells.

J-Pharmacol-Exp-Ther. 1998 Feb; 284(2): 768-76; ISSN: 0022-

3565.

UNITED-STATES. This study compared the interaction between

ethanol and gamma-aminobutyric acid (GABA)-mediated

current responses elicited in several immortalized cell lines

and stably transfected cells, as well as in cultured and acutely

dissociated rat cerebellar Purkinje cells. Only cell lines that

were found previously to possess functional GABAA receptors

were examined in this study. Under identical recording

conditions, ethanol (10-200 mM) exerted no effect on GABA-

induced currents in any of the cell lines or stably transfected

cells tested in this study. However, GABA responses monitored

in both primary culture and acutely dissociated Purkinje cells

were significantly potentiated by ethanol (25 and 50 mM).

Mouse pancreatic cells (RINm5F) were insensitive to both

diazepam and ethanol suggesting the expression of a GABAA

receptor isoform lacking a gamma subunit. Immortalized

neuroblastoma IMR-32 cells displayed GABA responses that

could be distinguished based on differential sensitivity to

diazepam. However, none of the IMR-32 cells displayed GABA

responses that were sensitive to modulation by ethanol. GABA

responses in the stably transfected cell lines, PA3

(alpha1beta1gamma2L) and WSS-1 (alpha1beta2gamma2), were

also unaffected by exposure to ethanol. In Purkinje cells

acutely dissociated from the neonatal cerebellum, the ethanol-

induced potentiation of GABA-induced current response could

be observed before postnatal day 7, when only the gamma2S

but not the gamma2L splice variant is expressed. This

indicates that the gamma2L subunit is not necessary for an

ethanol-induced potentiation of GABAA receptor-mediated

response to become manifest. In addition, the results point to

inherent differences that should be taken into account in

interpreting comparative data between native and recombinant

GABAA receptors.. 0; 40709-69-1; 485-49-4; 56-12-2; 64-

17-5.

167. Sargent, M. A.; Poskitt, K. J.; Jan, J. E. Congenital ocular motor

apraxia: imaging findings. AJNR-Am-J-Neuroradiol. 1997 Nov;

18(10): 1915-22; ISSN: 0195-6108.

UNITED-STATES. PURPOSE: To determine the frequency of

cerebellar and cerebral abnormalities on brain imaging studies

in children with congenital ocular motor apraxia. METHODS:

Brain imaging studies were performed in 19 children with

typical congenital ocular motor apraxia who were in the care

of a visual impairment program at a children's hospital.

Independent clinical review categorized the subjects as having

partial (n = 10) or expanded (n = 9) congenital ocular motor

apraxia on the basis of extent of associated speech or

neurodevelopmental problems. Fifteen CT studies and 13 MR

examinations of the brain performed in these children were

reviewed independently by two pediatric neuroradiologists.

Radiologic findings were agreed on by consensus. RESULTS:

Cerebellar abnormalities were found in 12 of 19 cases. The

cerebellar vermis was small in 10 children. A small cerebellar

vermis was the only abnormality in five of 10 children with

partial congenital ocular motor apraxia and in two of nine

children with expanded congenital ocular motor apraxia. Among

seven children with a small vermis examined with high-

resolution MR imaging, the inferior portion of the vermis was

preferentially involved in each case. Of these seven subjects,

none of four with partial congenital ocular motor apraxia but

two of three with expanded congenital ocular motor apraxia

had an abnormality of the superior portion of the vermis.

Miscellaneous supratentorial lesions affecting both gray and

white matter were found in six subjects. Five of the 19

children had normal imaging findings. CONCLUSION: Inferior

vermian hypoplasia is the most common abnormality in

children with congenital ocular motor apraxia.

168. Sastry, B. R.; Morishita, W.; Yip, S.; Shew, T. GABA-ergic

transmission in deep cerebellar nuclei. Prog-Neurobiol. 1997

Oct; 53(2): 259-71; ISSN: 0301-0082.

ENGLAND. gamma-Aminobutyric acid (GABA) is the inhibitory

transmitter released at Purkinje cell axon terminals in deep

cerebellar nuclei (DCN). Neurons in DCN also receive excitatory

glutamatergic inputs from the inferior olive. The output of DCN

neurons, which depends on the balance between excitation and

inhibition on these cells, is involved in cerebellar control of

motor coordination. Plasticity of synaptic transmission

observed in other areas of the mammalian central nervous

system (CNS) has received wide attention. If GABA-ergic

and/or glutamatergic synapses in DCN also undergo plasticity,

it would have major implications for cerebellar function. In

this review, literature evidence for GABA-ergic synaptic

transmission in DCN as well as its plasticity are discussed.

Studies indicate that fast inhibitory postsynaptic potentials

(IPSPs) and currents (IPSCs) in neurons of DCN are mediated by

GABAA receptors. While GABAB receptors are present in DCN,

they do not appear to be activated by Purkinje cell axons. The

IPSPs undergo paired-pulse, as well as frequency-dependent,

depressions. In addition, tetanic stimulation of inputs can

induce a long-term depression (LTD) of the IPSPs and IPSCs.

Excitatory synapses do not appear to undergo long-term

potentiation or LTD. The LTD of the IPSP is not input-specific,

as it can be induced heterosynaptically and is associated with

a reduced response of DCN neurons to a GABAA receptor

agonist. Postsynaptic Ca2+ and protein phosphatases appear to

contribute to the LTD. The N-methyl-D-aspartate receptor-

gated, as well as the voltage-gated Ca2+ channels are

proposed to be sources of the Ca2+. It is suggested that LTD of

GABA-ergic transmission, by regulating DCN output, can

modulate cerebellar function.. 56-12-2.

169. Schumacher, E. H.; Lauber, E.; Awh, E.; Jonides, J.; Smith, E. E.;

Koeppe, R. A. PET evidence for an amodal verbal working

memory system. Neuroimage. 1996 Apr; 3(2): 79-88; ISSN:

1053-8119.

UNITED-STATES. Current models of verbal working memory

assume that modality-specific representations are translated

into phonological representations before entering the working

memory system. We report an experiment that tests this

assumption. Positron emission tomography measures were

taken while subjects performed a verbal working memory task.

Stimuli were presented either visually or aurally, and a visual

or auditory search tasks, respectively, was used as a control.

Results revealed an almost complete overlap between the

active memory areas regardless of input modality. These areas

included dorsolateral frontal, Broca's area, SMA, and premotor

cortex in the left hemisphere; bilateral superior and posterior

parietal cortices and anterior cingulate; and right cerebellum.

These results correspond well with previous research and

suggest that verbal working memory is modality independent

and is mediated by a circuit involving frontal, parietal, and

cerebellar mechanisms.

170. Schwarz, M.; Alvarez Bolado, G.; Urbanek, P.; Busslinger, M.; Gruss,

P. Conserved biological function between Pax-2 and Pax-5 in

midbrain and cerebellum development: evidence from targeted

mutations. Proc-Natl-Acad-Sci-U-S-A. 1997 Dec 23; 94(26):

14518-23; ISSN: 0027-8424.

UNITED-STATES. The development of two major subdivisions

of the vertebrate nervous system, the midbrain and the

cerebellum, is controlled by signals emanating from a

constriction in the neural primordium called the

midbrain/hindbrain organizer (Joyner, A. L. (1996) Trends

Genet. 12, 15-201). The closely related transcription factors

Pax-2 and Pax-5 exhibit an overlapping expression pattern

very early in the developing midbrain/hindbrain junction.

Experiments carried out in fish (Krauss, S., Maden, M., Holder,

N. & Wilson, S. W. (1992) Nature (London) 360, 87-89) with

neutralizing antibodies against Pax-b, the orthologue of Pax-2

in mouse, placed this gene family in an regulatory cascade

necessary for the development of the midbrain and the

cerebellum. The targeted mutation of Pax-5 has been reported

to have only slight effects in the development of structures

derived from the isthmic constriction, whereas the Pax-2 null

mutant mice show a background-dependent phenotype with

varying penetrance. To test a possible redundant function

between Pax-2 and Pax-5 we analyzed the brain phenotypes of

mice expressing different dosages of both genes. Our results

demonstrate a conserved biological function of both proteins

in midbrain/hindbrain regionalization. Additionally, we show

that one allele of Pax-2, but not Pax-5, is necessary and

sufficient for midbrain and cerebellum development in

C57BL/6 mice.. 0; 0; 0; 0; 0.

171. Scuotto, A.; Cappabianca, S.; Melone, M. B.; Puoti, G. MRI "fogging"

in cerebellar ischaemia: case report. Neuroradiology. 1997 Nov;

39(11): 785-7; ISSN: 0028-3940.

GERMANY. Subacute cerebral infarcts may appear normal on

T2-weighted MRI as an area isointense with surrounding

normal tissue. This MRI "fogging effect" has been described in

only a few cases. We present a further case of fogging

observed during the evolution of a cerebellar infarct.

172. Shamoto, H.; Chugani, H. T. Glucose metabolism in the human

cerebellum: an analysis of crossed cerebellar diaschisis in

children with unilateral cerebral injury. J-Child-Neurol. 1997

Oct; 12(7): 407-14; ISSN: 0883-0738.

UNITED-STATES. Using high-resolution positron emission

tomography (PET), we have recently described the normal

pattern of glucose utilization in 11 anatomical regions of the

human cerebellum. In the present study, we evaluated the

phenomenon of crossed cerebellar diaschisis in 40 patients

(mostly children) with unilateral cerebral injury sustained at

various periods of brain development. Diaschisis refers to a

functional impairment at a remote site following injury to an

anatomically connected area of brain and, presumably due to a

loss of afferent input to the remote site. Of the 40 patients,

11 had sustained their cerebral injury prenatally, 7 in the

perinatal period (+/- 24 hours of birth), and 22 postnatally (1

day to 15 years). Crossed cerebellar hypometabolism was seen

in 22 patients; symmetric cerebellar metabolism was found in

16 subjects. The presence of crossed cerebellar

hypometabolism was typically associated (75% of cases) with

a postnatal injury, while symmetric cerebellar metabolism

was seen only in patients with injury occurring prior to 4

weeks of age (13 of the 16 had prenatal or perinatal insults). A

third pattern of cerebellar metabolism, consisting of

paradoxical crossed cerebellar hypermetabolism, was seen in

two patients; both had sustained their cerebral injury at 4

months of age. These findings suggest the presence of

considerable plasticity, which is dependent on age at injury, in

the cerebrocerebellar pathway of developing brain.. 50-99-7.

173. Simonati, A.; Dalla Bernardina, B.; Colombari, R.; Rizzuto, N.

Ponto-cerebellar hypoplasia with dystonia: clinico-

pathological findings in a sporadic case. Childs-Nerv-Syst.

1997 Nov; 13(11-12): 642-7; ISSN: 0256-7040.

GERMANY. Microcephaly, absent psychomotor development and

dystonic limb movements were the main clinical features of a

3-year-old girl affected by hypoplasia of the pontocerebellar

structures. As in the few previously reported cases there are

discrepancies between the severity of lesions in the

supratentorial and infratentorial compartments. Pathological

features such as size reduction of the ventral pons, inferior

olive atrophy, dentate nucleus fragmentation, and thinning of

the cerebellar cortex suggest an impaired maturation of the

involved structures due to a prenatal condition (dated at about

20-28 weeks of gestation). Somatotopic analysis failed to

provide conclusive evidence on the primary target of the

disease. The affected structures originate from the dorsal

rhombencephalic region at about the same gestational age, and

their maturation is probably under the control of sets of genes

which regulate pattern formation. Early abnormal functioning

of such genes might lead to the selected morphogenetical

alterations observed in ponto-cerebellar hypoplasia. The

normal morphogenetic pattern of the supratentorial structures

and the mild lesions observed suggest that their late

involvement can be related to a different pathogenetic

process.

174. Smith, A. M.; Mullen, R. J. Parallin, a cerebellar granule cell

protein the expression of which is developmentally regulated

by Purkinje cells: evidence from mutant mice. Brain-Res-Dev-

Brain-Res. 1997 Dec 19; 104(1-2): 79-89; ISSN: 0165-3806.

NETHERLANDS. In this paper we report on monoclonal antibody

3H6 with unique specificities for development of the

cerebellum. Immunohistochemical studies on normal and

mutant mice suggest that it is primarily located in or on

granule cell parallel fibers in the cerebellum. The only other

region showing immunoreactivity is a small region of the

hippocampus. The antigen is detected immunohistochemically

as early as postnatal day 11 in the molecular layer of the

cerebellum. In adult wild-type mice parallin expression is

seen in the molecular layer and to a lesser degree in the

internal granular layer. In the cerebella of two neurological

granule cell-deficient mutants, weaver (wv) and staggerer

(sg), parallin is not detected. However, in two Purkinje cell-

deficient mutants, Purkinje cell degeneration (pcd) and

nervous (nr), a more complex and interesting pattern is

observed. These two mutants do have granule cells and parallel

fibers and 3H6 immunoreactivity is observed. However, in both

of these Purkinje cell-deficient mutants the 3H6

immunoreactivity is drastically reduced in regions where

Purkinje cells have degenerated. Furthermore, in nr mutants,

the antigen appears to be concentrated in regions of the

parallel fiber that are in close proximity to Purkinje cells,

suggesting its possible association with synapses. Taken

together these results suggest that parallin is a marker of

granule cells and their parallel fibers, its onset correlates

with the formation of granule cell synapses on developing

Purkinje cells, and it requires Purkinje cells for the

maintenance of expression.. 0; 0.

175. Soha, J. M.; Kim, S.; Crandall, J. E.; Vogel, M. W. Rapid growth of

parallel fibers in the cerebella of normal and staggerer mutant

mice. J-Comp-Neurol. 1997 Dec 29; 389(4): 642-54; ISSN:

0021-9967.

UNITED-STATES. The growth of cerebellar granule cell axons

was examined by placing focal implants of 1,1',dioctadecyl-

3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) in the

cerebella of normal and staggerer mutant mice at a series of

developmental ages between postnatal day 2 (P2) and P30.

Parallel fibers contacting the implant site were brightly

labeled by the fluorescent dye, as were the associated granule

cell bodies located principally in the internal granule layer.

The extent of parallel fiber labeling in the molecular layer and

the distance from the implant to the most extreme labeled

granule cells were measured in sectioned material. Two

additional measures describing the distribution of labeled

granule cells about the implant site suggest length bounds for

most parallel fibers. Parallel fiber growth is surprisingly

rapid; all measures approached peak values at P3-P5, only a

few days after the earliest postmitotic granule cells

differentiate and migrate. At intermediate ages (P8 and P10),

parallel fiber lengths appeared to decrease transiently. At

later ages (P15 and beyond), the measures of fiber length

increased to their mature values. These values differed little

from lengths measured at P3-P5, suggesting that most

parallel fiber growth occurs within a few days of cell birth. At

early and intermediate ages, parallel fiber lengths in

staggerer mice were comparable to controls, suggesting that

an interaction with normal healthy Purkinje cells is not

essential for parallel fiber outgrowth.. 0; 0; 40957-95-7.

176. Sorenson, E. J.; Wijdicks, E. F.; Thielen, K. R.; Cheng, T. M. Acute

bilateral infarcts of the posterior inferior cerebellar artery.

J-Neuroimaging. 1997 Oct; 7(4): 250-1; ISSN: 1051-2284.

UNITED-STATES. Acute bilateral infarcts in the territory of

the posterior inferior cerebellum artery are rare and poorly

documented in the literature. Thus, this report describes the

clinical course and outcome in 3 patients. Although one was

associated with coronary artery bypass surgery, the etiology

was not known. Despite large territorial infarcts, the patients

recovered to ambulation with minimal assistance.

177. Southan, A. P.; Robertson, B. Patch-clamp recordings from

cerebellar basket cell bodies and their presynaptic terminals

reveal an asymmetric distribution of voltage-gated potassium

channels. J-Neurosci. 1998 Feb 1; 18(3): 948-55; ISSN: 0270-

6474.

UNITED-STATES. Cerebellar basket cells form highly

specialized inhibitory synaptic contacts with Purkinje cells,

namely the pericellular basket and pinceau nerve terminal

structures, wrapping around the Purkinje cell somatic and

axon hillock regions. These inhibitory synaptic contacts are

ideally located to control the ultimate output of the cerebellar

cortex. Previous immunohistochemical studies have shown

that these synaptic structures possess a very high density of

the dendrotoxin (DTX)-sensitive potassium channel subunit,

Kv1.2. We have taken advantage of this unique anatomical

arrangement offering a high concentration of identified Kv

channel subunits by combining whole-cell patch-clamp

recording and fluorescence microscopy to establish a novel

preparation and perform the first recordings from

unambiguously identified mammalian CNS inhibitory

presynaptic terminals. We report that DTX-sensitive

potassium channels are present in basket cell terminals but

not in the basket cell soma. This selective cellular

distribution suggests that these channels play an important

role in modulating cerebellar inhibitory synaptic

transmission.. 0; 0; 4368-28-9; 7440-09-7; 7440-23-5;

74811-93-1.

178. Stangel, M.; Luchow, A.; Stapf, C.; Marx, P.; Mohr, J. P.; Mast, H.

Cerebellar atrophy with basilar artery occlusion. Eur-J-Med-

Res. 1997 Oct 30; 2(10): 428-30; ISSN: 0949-2321.

GERMANY. Small and large vessel occlusive disease leading to

chronic cerebral ischemia and brain atrophy is a concept

originating in the last century. The modern notion of acute

brain infarct, however, appears to have eclipsed the idea of

chronic hypoperfusion as an important factor in ischemic

cerebral damage. We present a patient history featuring

recurrent episodes of acute posterior circulation

infratentorial ischemia in addition to a progressive cerebellar

syndrome over a course of several years. Laboratory work-up

including cerebral angiography, repeated CT and MR scanning

revealed basilar artery occlusion, a pontine infarct and a

subsequently developing cerebellar atrophy without signs of

cerebellar infarction. Findings indicating causes of cerebellar

atrophy other than ischemia could not be elicited. We offer the

hypothesis that basilar artery occlusion, inducing subsequent

chronic ischemia, is the most likely cause of the cerebellar

atrophy observed in our case.

179. Stone, J. A.; Chakeres, D. W.; Schmalbrock, P. High-resolution MR

imaging of the auditory pathway. Magn-Reson-Imaging-Clin-N-

Am. 1998 Feb; 6(1): 195-217; ISSN: 1064-9689.

UNITED-STATES. MR imaging is a valuable tool in the

evaluation of the auditory pathway. The current techniques in

high-resolution MR imaging of the temporal bone are presented

followed by a review of normal anatomy. Several diseases

involving the middle ear, inner ear, internal auditory canal, and

cerebellopontine angle are then presented. A radiologic-

pathologic approach is used to illustrate the nature of these

diseases and their appearance on MR imaging.

180. Street, V. A.; Bosma, M. M.; Demas, V. P.; Regan, M. R.; Lin, D. D.;

Robinson, L. C.; Agnew, W. S.; Tempel, B. L. The type 1 inositol

1,4,5-trisphosphate receptor gene is altered in the

opisthotonos mouse. J-Neurosci. 1997 Jan 15; 17(2): 635-45;

ISSN: 0270-6474.

UNITED-STATES. The opisthotonos (opt) mutation arose

spontaneously in a C57BL/Ks-db2J colony and is the only

known, naturally occurring allele of opt. This mutant mouse

was first identified based on its ataxic and convulsive

phenotype. Genetic and molecular data presented here

demonstrate that the type 1 inositol 1,4,5-trisphosphate

receptor (IP3R1) protein, which serves as an IP3-gated

channel to release calcium from intracellular stores, is

altered in the opt mutant. A genomic deletion in the IP3R1

gene removes two exons from the IP3R1 mRNA but does not

interrupt the translational reading frame. The altered protein

is predicted to have lost several modulatory sites and is

present at markedly reduced levels in opt homozygotes.

Nonetheless, a strong calcium release from intracellular

stores can be elicited in cerebellar Purkinje neurons treated

with the metabotropic glutamate receptor (mGluR) agonist

quisqualate (QA). QA activates Group 1 mGluRs linked to GTP-

binding proteins that stimulate phospholipase C and

subsequent production of the intracellular messenger IP3,

leading to calcium mobilization via the IP3R1 protein. The

calcium response in opt homozygotes shows less attenuation

to repeated QA application than in control littermates. These

data suggest that the convulsions and ataxia observed in opt

mice may be caused by the physiological dysregulation of a

functional IP3R1 protein.. EC 3.1.4.10; EC 3.1.4.3; 0; 0; 0; 0; 0;

0; 52809-07-1; 7440-70-2.

181. Tagliati, M.; Simpson, D.; Morgello, S.; Clifford, D.; Schwartz, R. L.;

Berger, J. R. Cerebellar degeneration associated with human

immunodeficiency virus infection. Neurology. 1998 Jan; 50(1):

244-51; ISSN: 0028-3878.

UNITED-STATES. Cerebellar disorders associated with HIV

infection are typically the result of discrete cerebellar

lesions resulting from opportunistic infections such as

toxoplasmosis and progressive multifocal leukoencephalopathy

or primary CNS lymphoma. Clinical symptoms and pathologic

abnormalities related to the cerebellum may also be observed

with HIV dementia. A primary cerebellar degeneration with

HIV has not previously been reported. Ten patients were

identified over an 8-year period at five medical centers. All

patients had clinical, laboratory, and radiologic evaluations,

and three had neuropathologic examinations. Patients

presented with progressively unsteady gait, slurred speech,

and limb clumsiness. Examination revealed gait ataxia,

impaired limb coordination, dysarthria, and abnormal eye

movements. Cognition, strength, and sensory function remained

normal. CD4 lymphocyte counts varied between 10 and 437

cells/mm3. Neuroimaging studies showed prominent cerebellar

atrophy. Neuropathology showed focal degeneration of the

cerebellar granular cell layer and unusual focal axonal

swellings in the brainstem and spinal cord. Cultures,

histopathology, and immunochemical studies showed no

conclusive evidence of infection. We report a syndrome of

unexplained degeneration of the cerebellum occurring in

association with HIV infection.

182. Takacs, J.; Gombos, G.; Gorcs, T.; Becker, T.; de Barry, J.; Hamori,

J. Distribution of metabotropic glutamate receptor type 1a in

Purkinje cell dendritic spines is independent of the presence

of presynaptic parallel fibers. J-Neurosci-Res. 1997 Nov 1;

50(3): 433-42; ISSN: 0360-4012.

UNITED-STATES. The metabotropic glutamate receptor type 1a

(mGluR1a) is expressed at a high level in the molecular layer

of the cerebellar cortex, where it is localized mostly in

dendritic spines of Purkinje cells, innervated by parallel

fibers. Treatment with methylazoxymethanol (MAM) of mouse

pups at postnatal days (PND) 0 + 1 or 5 + 6 results in the

partial loss of granule cells, the extent of which depends on

the age of the animal at the time of injection. As a

consequence of hypogranularity, the number of parallel fibers

is decreased to such an amount that many of the postsynaptic

Purkinje cell dendritic spines are devoid of axonal input, and

only a limited number of spines participate in the formation of

parallel fiber synapses, or, infrequently, in heterologous or

heterotopic synapses with other presynaptic partners. At PND

30, 50% of the spines in the cerebella of mice treated with

MAM at PND 0 + 1 was not contacted by any presynaptic

element, compared to 5% in controls or 15% in the cerebella of

mice treated with MAM at PND 5 + 6. The localization of

mGluR1a was visualized by immunocytochemistry on ultrathin

sections: approximately 80% of all Purkinje cell dendritic

spines were immunopositive in controls and in both groups of

MAM-treated mice, indicating that mGluR1a was present in

Purkinje dendritic spines even when the corresponding

synaptic input was absent. This observation indicates that the

expression and subcellular distribution of mGluR1a are

inherent, genetically determined properties of Purkinje cells..

0; 0; 0; 590-96-5; 592-62-1.

183. Tanaka, J.; Ichikawa, R.; Watanabe, M.; Tanaka, K.; Inoue, Y. Extra-

junctional localization of glutamate transporter EAAT4 at

excitatory Purkinje cell synapses. Neuroreport. 1997 Jul 28;

8(11): 2461-4; ISSN: 0959-4965.

ENGLAND. We used silver-enhanced immunogold electron

microscopy to reveal synaptic localization of the glutamate

transporter EAAT4 in mouse cerebellar Purkinje cells (PCs).

Gold-silver particles representing the EAAT4 were densely

localized on extra-junctional membrane, but not on junctional

membrane of PC spines in contact with parallel fiber or

climbing fiber terminals. No particle accumulations were

observed at inhibitory synapses formed on cell body and

dendritic shafts of PCs. Therefore, the EAAT4 is selectively

targeted to the extra-junctional site of excitatory PC

synapses. The finding suggests that the EAAT4 transports

glutamate or its related amino acids from outside the synaptic

cleft, which would facilitate glutamate diffusion from the

synaptic cleft to the extrasynaptic space and restrict

glutamate spillover to adjacent synapses.. 0; 0; 56-86-0.

184. Tanaka, S.; Tanaka, M.; Wada, N.; Okamoto, K.; Hirai, S.; Tanaka, K.

[Uncoupling of cerebellar blood flow and metabolism in

paraneoplastic cerebellar degeneration: report of a case].

Rinsho-Shinkeigaku. 1997 Jun; 37(6): 514-9; ISSN: 0009-918X.

JAPAN. We report a 65-year-old woman with paraneoplastic

cerebellar degeneration (PCD) who showed reduced cerebellar

metabolism with preserved blood flow. She was admitted to

Gunma University Hospital because of progressive gait and

speech disturbances. Neurologic examination revealed

nystagmus, dysphagia, explosive speech, reduced muscle tone

in limbs, and marked truncal and limb ataxia, and mild

hypesthesia in hands and feet. Cranial MRI demonstrated slight

cerebellar atrophy. Laboratory findings disclosed high levels

of serum CA19-9 and other tumor markers, and positive anti-

Yo antibody, indicating that she had PCD. A specimen obtained

from an axillary lymph node revealed metastasis of poorly

differentiated adenocarcinoma, although systemic and

vigorous checkup failed to find its origin. Cerebral blood flow

(CBF) and cerebral metabolic rate of oxygen (CMRO2) were

measured using positron emission tomography (PET) 15 months

after the onset. CMRO2 was clearly decreased in the

cerebellum, while CBF was almost normal. Moreover, PET with

2 18F-fluoro-2-deoxy-D-glucose (FDG) revealed that glucose

metabolism was also reduced in the cerebellum. Single photon

emission tomography using 99mTc-ethyl cysteinate dimer

(ECD) showed a normal blood flow pattern in the whole brain.

These results indicated that uncoupling of circulation and

metabolism in the cerebellum of this patient. There are

several reports showing uncoupling of cerebral perfusion and

metabolism in ischemic disorders, encephalitis, mitochondrial

diseases, brain tumors, epilepsy and Gaucher disease, although

its pathophysiology is not elucidated. Because anti-Yo antibody

evidently gives a suppressive influence on the cerebellar

neurons, understanding the way the autoantibody acts may give

a clue to the mechanism of reduced cerebellar metabolism

with preserved perfusion in PCD.. 0.

185. Tian, J. r.; Lynch, J. C. Subcortical input to the smooth and

saccadic eye movement subregions of the frontal eye field in

Cebus monkey. J-Neurosci. 1997 Dec 1; 17(23): 9233-47; ISSN:

0270-6474.

UNITED-STATES. We have recently identified two functional

subregions in the frontal eye field (FEF) of the Cebus monkey, a

smooth eye movement subregion (FEFsem) and a saccadic

subregion (FEFsac). The thalamic input to these two subregions

was studied and quantified to gain more information about the

influence of the cerebellum and basal ganglia on the

oculomotor control mechanisms of the cerebral cortex. A

recent study using transneuronal transport of virus

demonstrated that there are neurons in the basal ganglia and

cerebellum that project to the FEFsac with only a single

intervening synapse (Lunch et al., 1994). In the present study,

we concentrated on the thalamic input to the FEFsem to define

possible basal ganglia-thalamus-cortex and cerebellum-

thalamus-cortex channels of information flow to the FEFsem.

We localized the functional subregions using low threshold

microstimulation, and retrogradely transported fluorescent

tracers were then placed into the FEFsem and FEFsac. The

neurons that project to the FEFsem are distributed in (1) the

rostral portion of the ventral lateral nucleus, pars caudalis,

(2) the caudal portion of the ventral lateral nucleus, pars

caudalis, (3) the mediodorsal nucleus, (4) the ventral anterior

nucleus, pars parvocellularis, and (5) the ventral anterior

nucleus, pars magnocellularis. In contrast, the large majority

of neurons that project to the FEFsac are located in the

paralaminar region of the mediodorsal nucleus. The FEFsac and

FEFsem thus each receive neural input from both basal

ganglia-receiving and cerebellar-receiving cell groups in the

thalamus, but each receives input from a unique combination

of thalamic nuclei.. 0.

186. Timofeev, I.; Steriade, M. Fast (mainly 30-100 Hz) oscillations in

the cat cerebellothalamic pathway and their synchronization

with cortical potentials. J-Physiol-Lond. 1997 Oct 1; 504( Pt

1): 153-68; ISSN: 0022-3751.

ENGLAND. 1. Intracellular recordings from 216

thalamocortical (TC) neurones in the ventrolateral (VL)

nucleus of intact-cortex and decorticated cats under

ketamine-xylazine anaesthesia revealed spontaneously

occurring fast oscillations (mainly 30-100 Hz) in 86% of

investigated cells. The fast depolarizing events consisted of

excitatory postsynaptic potentials (EPSPs), giving rise to fast

prepotentials (FPPs) in 22% of neurones, which eventually lead

to full-blown action potentials. The frequency of fast events

changed by factors of 2-5 in periods as short as 0.3-1.0 s. 2.

The spontaneous oscillations were similar to responses evoked

in VL relay neurones by stimuli to the afferent cerebellofugal

axons in brachium conjunctivum (BC) and were strikingly

reduced or abolished after electrolytic lesion of BC axons. 3.

The amplitude and duration of fast depolarizing events were

significantly reduced during the descending phase of the

inhibitory postsynaptic potentials (IPSPs) in TC cells, related

to spontaneous spindles or evoked by local thalamic

stimulation. 4. Averaged field potentials recorded from motor

cortex and triggered by EPSPs and/or action potentials of

intracellularly recorded VL cells demonstrated that both

spontaneous and BC-evoked fast depolarizations in VL relay

neurones were coherent with fast rhythms in cortical area 4.

5. These results show that, in addition to the thalamic and

cortical generation sites of the fast (so-called gamma)

oscillations, prethalamic relay stations, such as deep

cerebellar nuclei, are major contributors to the induction of

fast rhythms which depend on the depolarization of thalamic

and cortical neurones and which represent a hallmark of brain

activation patterns.

187. Torres Aleman, I.; Villalba, M.; Nieto Bona, M. P. Insulin-like

growth factor-I modulation of cerebellar cell populations is

developmentally stage-dependent and mediated by specific

intracellular pathways. Neuroscience. 1998 Mar; 83(2): 321-

34; ISSN: 0306-4522.

UNITED-STATES. Although development of transgenic animals

overexpressing insulin-like growth factor-I has allowed the

establishment of a role of this trophic factor in brain growth,

detailed knowledge of the action of insulin-like growth

factor-I on different brain areas is still lacking. We now

provide evidence for a pleiotrophic role of this growth factor

on cerebellar development. Insulin-like growth factor-I

produced by cerebellar cultures is a survival factor for

Purkinje cells and a mitogen/differentiation factor for

cerebellar glioblasts. Trophic effects of insulin-like growth

factor-I were observed only during specific developmental

stages. In addition, insulin-like growth factor-I increased

intracellular Ca2+ levels in Purkinje cells and c-Fos in

dividing glioblasts. Survival-promoting effects of insulin-like

growth factor-I on Purkinje cells required activation of

protein kinase C, while glioblast division induced by insulin-

like growth factor-I depended on phosphatidylinosytol 3-

kinase activation. We conclude that insulin-like growth

factor-I is a paracrine/autocrine pleiotrophic factor for both

glia and neurons in the cerebellum. Its effects are mediated by

distinct intracellular signals and appear to be specific to the

developmental stage of the target cell. Since development of

the different cell populations that compose a specific brain

territory is not synchronized, the pleiotrophic action of

growth factors such as insulin-like growth factor-I may be

essential to ontogenetic processes underlying normal brain

growth.. EC 2.7.1.137; 0; 50-89-5; 67763-96-6; 7440-70-2.

188. Townsend, J.; Harris, N. S.; Courchesne, E. Visual attention

abnormalities in autism: delayed orienting to location. J-Int-

Neuropsychol-Soc. 1996 Nov; 2(6): 541-50; ISSN: 1355-6177.

ENGLAND. These studies provide evidence for slowed spatial

orienting of attention in autism. A group of well-defined adult

autistic subjects and age-matched normal controls performed

a traditional spatial cueing task in which attention-related

response facilitation is indexed by speed of target detection.

To address the concern that motor impairment may interfere

with interpretation of response time measures in those with

neurologic abnormality, we also used a new adaptation of the

traditional task that depended on accuracy of response (target

discrimination) rather than speed of response. This design

allowed separation of time to process and respond to target

information from the time to move and engage (orient)

attention. Results from both tasks were strikingly similar.

Normal subjects oriented attention very quickly, and showed

maximal performance facilitation at a cued location within

100 ms. Autistic subjects oriented attention much more

slowly and showed increasing benefits of a spatial cue with

increasing cue-to-target delays. These results are consistent

with previous reports that patients with autism, the majority

of whom have developmental abnormalities of the cerebellum,

as well as those with acquired damage to the cerebellum, are

slow to shift attention between and within modalities. This

paper also addresses the variability in behavioral findings in

autism, and suggests that many of the apparently

contradictory findings may actually reflect sampling

differences in patterns of brain pathology.

189. Traiffort, E.; Charytoniuk, D. A.; Faure, H.; Ruat, M. Regional

distribution of Sonic Hedgehog, patched, and smoothened mRNA

in the adult rat brain. J-Neurochem. 1998 Mar; 70(3): 1327-30;

ISSN: 0022-3042.

UNITED-STATES. In vertebrates, Sonic Hedgehog (Shh), Desert

Hedgehog (Dhh), and Indian Hedgehog (Ihh) genes encode a

family of morphogen proteins that are implicated in a wide

range of signaling activities, particularly during embryonic

development. These secreted proteins are proposed to mediate

their effects on target cells by interacting with their putative

receptor, Patched (Ptc), and with a seven-pass transmembrane

protein, Smoothened (Smo). However, the roles that these

signaling molecules may play in adult tissues, particularly in

brain, are not yet clearly defined. Therefore, we investigated

the expression of these genes in adult rat tissues. Northern

blot analysis revealed expression of Shh, Dhh, and Ihh genes in

peripheral tissues, whereas Shh transcript was also identified

in brain. It is interesting that northern blot analysis with

probes derived from the mouse Ptc and Smo genes revealed the

expression of a 7.9-kb and a 3.7-kb transcript, respectively, in

all brain tissues examined. In situ hybridization experiments

using specific digoxigenin-labeled riboprobes showed

expression of Ptc and Smo transcripts in discrete brain areas.

Shh-positive cells were observed in restricted regions of the

brain. Within the cerebellum, Shh, Ptc, and Smo transcripts

were colocalized in the Purkinje cell layer. These data suggest

that, besides its roles in determining cell fate and patterning

during embryogenesis, the hedgehog signaling pathway may

have also important roles in the adult brain.. 0; 0; 0; 0; 0; 0; 0;

0.

190. Tsaur, M. L.; Wan, Y. C.; Lai, F. P.; Cheng, H. F. Expression of B-type

endothelin receptor gene during neural development. FEBS-Lett.

1997 Nov 10; 417(2): 208-12; ISSN: 0014-5793.

NETHERLANDS. Mutations of the B-type endothelin receptor

(ETRB) gene have been found to cause defects in the

development of enteric neurons, which resulted in aganglionic

megacolon in rodents and humans. To determine the

distribution of ETRB mRNA during neural development, mainly

in the CNS, in situ hybridization was applied at various

developmental stages of rat. ETRB gene was abundantly

expressed prenatally in the ventricular and subventricular

zones, as well as postnatally in the ependymal and

subependymal cells. ETRB mRNA was also strongly detected

prenatally in the dorsal root ganglia, as well as postnatally in

the cerebellar Bergmann glial cells and epithelial cells of

choroid plexus. Our data suggest that ETRB acts as a regulator

in the differentiation, proliferation, or migration of neural

cells during development.. 0; 0; 0.

191. Ueyama, T.; Tamaki, N.; Kondoh, T.; Kokunai, T.; Asada, M.

Cerebellopontine angle ependymoma with internal auditory

canal enlargement and pineal extension--case report. Neurol-

Med-Chir-Tokyo. 1997 Oct; 37(10): 762-5; ISSN: 0470-8105.

JAPAN. A 38-year-old male presented with a posterior fossa

ependymoma with unusual extension from the cerebellopontine

angle to the pineal region. Magnetic resonance imaging clearly

demonstrated that these two components were continuous

through the right ambient cistern. Computed tomography using

a bone algorithm revealed enlargement of the right internal

auditory canal. This case suggests that ependymoma can

extend anywhere within the subarachnoid space along the path

of least resistance.

192. Undar, A.; Lodge, A. J.; Daggett, C. W.; Runge, T. M.; Ungerleider, R.

M.; Calhoon, J. H. Error associated with the choice of an aortic

cannula in measuring regional cerebral blood flow with

microspheres during pulsatile CPB in a neonatal piglet model.

ASAIO-J. 1997 Sep; 43(5): M482-6; ISSN: 1058-2916.

UNITED-STATES. The effectiveness of an infant pulsatile

cardiopulmonary bypass (CPB) system on maintaining regional

cerebral blood flow (CBF) using two different types of aortic

cannulae in 3 kg piglets has been investigated. The University

of Texas Neonatal Pulsatile Pump was used with either a DLP

(Group I, n = 6) or an Elecath (Group II, n = 7) 10Fr aortic

cannula. In all the subjects, nasopharyngeal temperature was

reduced to 18 degrees C, followed by 1 hr of deep hypothermic

circulatory arrest (DHCA), then 45 min of rewarming. During

cooling and rewarming, alpha-stat blood gas management was

used. The radionuclide labeled microsphere technique was used

to determine blood flows in the cerebellum, basal ganglia,

brainstem, right and left hemispheres, as well as global CBF

(ml/100 g/min). When the DLP aortic cannula was used,

regional and global CBF appeared to be higher pre- and post

DHCA. In both groups regional CBF was significantly decreased

following DHCA. Although better pulsatile flow was attained

using the DLP cannula and this may have resulted in higher

regional CBF, these results must be interpreted in light of the

large standard deviations noted when this cannula was chosen

for the studies. These results demonstrate the importance of

choosing an appropriate aortic cannula for measuring regional

CBF with a pulsatile neonate-infant CPB system.

193. Vajtai, I.; Varga, Z. Origin of de novo central nervous system

cavernomas [letter]. J-Neurosurg. 1998 Mar; 88(3): 616-7;

ISSN: 0022-3085.

UNITED-STATES.

194. van Mourik, M.; Catsman Berrevoets, C. E.; Paquier, P. F.; Yousef,

Bak E.; van Dongen, H. R. Acquired childhood dysarthria: review

of its clinical presentation. Pediatr-Neurol. 1997 Nov; 17(4):

299-307; ISSN: 0887-8994.

UNITED-STATES. The adult classification of dysarthria

correlating with the pathophysiology of the motor systems is

usually applied to classify acquired childhood dysarthria.

However, the validity of this adult model for children has not

been studied systematically. All studies pertaining to analysis

of speech features in acquired childhood dysarthria published

since 1980 were reviewed. Studies were classified on the

basis of neuroradiologic evidence of lesion site and associated

motor disorder. This review demonstrates that knowledge of

acquired childhood dysarthria is based on a limited number of

single case studies, most of which pertain to dysarthria

occurring after resection of cerebellar tumor. Definite

similarities to adult dysarthria were not evident. Some

similarity to acquired childhood dysarthria due to basal

ganglia lesions was detected. We conclude that acquired

childhood dysarthria requires its own classification.

195. Van Nechel, C. [Adaptation of the central nervous system to

optical correction]. Adaptation du systeme nerveux central

aux corrections optiques. Bull-Soc-Belge-Ophtalmol. 1997;

264: 99-103; ISSN: 0081-0746.

BELGIUM. Wearing spectacles imply an adjustment of the

visual perception and eye movements. The visual cortex

accounts for this plasticity, including at the adulthood,

especially by the shift or the sprading of the receptor fields

and the adjustment of the sensitivity of the primary visual

cortex cells to spatial orientation and movement. The

cerebellum modulates the vestibulo-ocular reflex gain. The

adjustment latencies range from a few minutes to several

days according to the disturbancy severity, the drug

interferences and the age and medical history of the subject.

Neurotrophins seem to be essential for this adjustment and

might become an efficient tool to extend the plasticity period..

0; 0.

196. Velier, J. J.; Ellison, J. A.; Fisher, R. S.; Vinters, H. V. The trkC

receptor is transiently localized to Purkinje cell dendrites

during outgrowth and maturation in the rat. J-Neurosci-Res.

1997 Nov 15; 50(4): 649-56; ISSN: 0360-4012.

UNITED-STATES. In vivo studies of granule cell gene

expression during corticocerebellar development and in vitro

studies of Purkinje cell neurite outgrowth suggest that

neurotrophin-3 may influence growth of Purkinje cell

dendrites. To determine whether neurotrophic substances

affect the growth of specific neuronal processes (i.e. axons

and dendrites) or nonspecifically cause process development

by exerting a trophic influence upon neuronal physiology we

performed an immunohistochemical examination of trkC

protein expression during early postnatal development of the

rat cerebellum. Our findings indicate that Purkinje cells begin

to synthesize trkC protein coincident with the onset of

dendritic outgrowth. Robust immunostaining was evident

throughout the entire somatodendritic domain of Purkinje

cells during dendritic development but became faint and

restricted to the cell body subsequent to the completion of

dendritogenesis. These results suggest that growth and

maturation of the Purkinje cell dendritic arbor may be

influenced by neurotrophin-3 activation of trkC receptors

distributed within developing dendrites.. EC 2.7.1.-; 0; 0;

144515-70-8.

197. Vigot, R.; Batini, C. GABA(B) receptor activation of Purkinje cells

in cerebellar slices. Neurosci-Res. 1997 Oct; 29(2): 151-60;

ISSN: 0168-0102.

IRELAND. The metabotropic GABA(B) receptors are densely

represented in the molecular layer of the cerebellar cortex

which contains the dendritic tree of the Purkinje cells (PCs).

We report here the results obtained by applying Baclofen, the

specific GABA(B) agonist, to PCs recorded intrasomatically in

cerebellar slices. Diluted in the perfusion solution or applied

by pressure to the molecular layer near to the recorded cell,

Baclofen dose-dependently inhibited the PCs as seen by the

suppression of Na and Ca dependent action potentials

accompanied by a variable membrane hyperpolarization. The

weak hyperpolarization was interpreted as due to the dendritic

localization of the receptors. These results concerned

postsynaptic receptor sites since they persisted after bath

applied TTX blocking presynaptic activity. They also persisted

in the presence of bicuculline, the GABA(A) antagonist, but

they were reduced by bath application of 2-OH saclofen and

CGP55845A, both being GABA(B) receptor antagonists. Current

clamp experiments revealed a conductance increase with an

equilibrium potential consistent with a K+ channel opening.

The conclusions were reached that GABA inhibition of the PCs

is mediated by GABA(B) receptors in the dendrites and

GABA(A) receptors in the soma and dendrites. Therefore, the

GABA released by stellate cells modulate PC activity through

two inhibitory mechanisms.. 0; 0; 0; 0; 0; 1134-47-0;

117354-64-0; 148056-42-2; 7440-09-7.

198. Wall, R. J. Subarachnoid haemorrhage presenting as postoperative

neck pain [letter]. Anaesth-Intensive-Care. 1997 Oct; 25(5):

578; ISSN: 0310-057X.

AUSTRALIA.

199. Wegmann, C.; Munzenmaier, R.; Dormann, A. J.; Huchzermeyer, H.

[Ticlopidine-induced acute cholestatic hepatitis]. Ticlopidin-

induzierte akute cholestatische Hepatitis. Dtsch-Med-

Wochenschr. 1998 Feb 6; 123(6): 146-50; ISSN: 0012-0472.

GERMANY. HISTORY AND ADMISSION FINDINGS: A 52-year-old

man who had sustained a cerebellar infarct was given the

platelet inhibitor ticlopidine (2 x 250 mg/d) to prevent further

thromboses. 28 days after starting the medication he

complained of itchings, feeling unwell and diarrhoea. He had

also noted darkened urine and faecal discoloration. Physical

examination revealed marked jaundice and multiple scratch

marks over the entire body. INVESTIGATIONS: The activities in

serum of alkaline phosphatase (420 U/l) and of gamma-GT

(470 U/l) were markedly elevated and total bilirubin

concentration was maximally 26.4 mg/dl. Activities of GPT

(197 U/l) and GOT (44 U/l) were slightly increased. No cause

was found for any extra- or intrahepatic cholestasis with or

without mechanical obstruction (e.g. viral or autoimmune

hepatitis). A biopsy, which showed centro-acinar cholestasis

also suggested drug-induced liver damage. TREATMENT AND

COURSE: Despite discontinuing ticlopidine, the signs of

cholestatic hepatitis had only disappeared 2 1/2 months after

the onset of symptoms. CONCLUSION: Changes in the blood

picture, allergic skin reactions and gastrointestinal disorders

are among the significant clinical side effects of ticlopidine.

As this drug is increasingly being prescribed world-wide, the

possibility of toxic liver damage should be taken into account..

EC 2.3.2.2; EC 2.6.1.1; EC 2.6.1.2; EC 3.1.3.1; 0; 55142-85-3;

635-65-4.

200. Widdowson, P. S.; Gyte, A.; Upton, R.; Smith, J. C.; Pitts, M.;

Moores, R.; Wyatt, I. L-2-chloropropionic acid-induced

cerebellar granule cell necrosis is potentiated by L-type

calcium channel antagonists. Arch-Toxicol. 1997; 71(12): 751-

5; ISSN: 0340-5761.

GERMANY. We have used the model of L-2-chloropropionic acid

(L-CPA)-induced selective cerebellar granule necrosis to study

excitatory amino acid-induced necrotic cell death in vivo

produced by the activation of N-methyl-D-aspartate (NMDA)

receptors. However, the mechanism for the NMDA receptor

activation and the biochemical events which dictate the

anatomical selectivity for the L-CPA-induced lesion are as yet

unknown. We examined whether blockade of sodium and

calcium channels may reduce the neurotoxicity through a

reduction of glutamate release from granule cells. None of the

sodium channel antagonists examined, i.e. phenytoin,

lamotrigine or rilazole nor the mixed sodium/calcium channel

blocker, lifarazine, altered the L-CPA neurotoxicity. However,

L-type calcium channel blockers, verapamil and nifedipine

enhanced the L-CPA-induced granule cell necrosis, assessed by

measuring the degree of L-CPA-induced reductions in

cerebellar aspartate concentration, increases in cerebellar

glycine concentrations and the development of cerebellar

oedema. In addition, the locomotor activity of rats receiving

both L-CPA and either verapamil or nifedipine was

significantly lower than when rats received L-CPA alone,

suggesting an enhancement of the neurotoxicity of L-CPA by L-

type calcium channel blockade. The data suggest that L-CPA

may interfere with non-L-type calcium channels located on

granule cell bodies and nerve terminals leading to reduction of

the calcium entry into the cells. We suggest that a

combination of L-type channel blockade and non-L-type

channels which are sensitive to L-CPA produces reductions in

intracellular calcium concentrations below that required for

neuronal survival.. 0; 0; 21829-25-4; 52-53-9; 56-40-6; 56-

84-8; 598-78-7; 7440-23-5.

201. Willbold, E.; Berger, J.; Reinicke, M.; Wolburg, H. On the role of

Muller glia cells in histogenesis: only retinal spheroids, but

not tectal, telencephalic and cerebellar spheroids develop

histotypical patterns. J-Hirnforsch. 1997; 38(3): 383-96; ISSN:

0021-8359.

GERMANY. The establishment of cell and fibre layers and the

specification of different cell types are crucial processes

during development of the central nervous system. Here we

investigated the developmental architecture of radial glia

cells in these processes using so-called spheroids that arise

from dissociated chicken embryonic neural cells in rotation

culture. We were able to produce retinal, tectal, and

telencephalic spheroids from E6 embryos and cerebellar

spheroids from E10 embryos. Cell and fibre differentiation can

be observed in all types of spheroids, however, it is most

abundant in retinal spheroids. Moreover, only in retinal

spheroids a histotypic organization can be detected. Using

immunohistochemistry and electron microscopy, we assign

this -at least partially- to the capacity of Muller cells to form

radial scaffolds, since we observe a congruency between these

radial scaffolds and the presence of rosettes formed by

photoreceptor precursors and Muller cells. Tectal,

telencephalic and cerebellar spheroids do not show organized

radial glia scaffolds, instead, the radial glia cells are

randomly arranged and the spheroids do not show histotypical

organization. The application of the specific gliotoxin 6-

aminonicotinamide to growing retinal spheroids leads to a

significant decrease in the number and size of the rosettes.

Concomitantly, the degree of histotypical organization is also

drastically reduced. This organizing capacity of Muller cells in

vitro now strongly suggests the presence of a comparable

function also in vivo. Moreover, since non-retinal radial glia

cells are not able to re-organize an histotypic organization in

vitro, Muller cells seem to be qualitatively different from

other radial glia cells. In future studies we want to untangle

these differences.. 0.

202. Wisden, W.; Moss, S. J. gamma-Aminobutyric acid type A receptor

subunit assembly and sorting: gene targeting and cell biology

approaches. Biochem-Soc-Trans. 1997 Aug; 25(3): 820-4; ISSN:

0300-5127.

ENGLAND. 0; 0.

203. Woelfle, J.; Haverkamp, F.; Kreft, B. Repeated syncopes and

extended paediatric hydrosyringomyelia/Chiari I malformation:

relation or coincidence? [letter]. J-Neurol-Neurosurg-

Psychiatry. 1998 Feb; 64(2): 278-9; ISSN: 0022-3050.

ENGLAND.

204. Wood, A. M.; Bristow, D. R. N-methyl-D-aspartate receptor

desensitisation is neuroprotective by inhibiting glutamate-

induced apoptotic-like death. J-Neurochem. 1998 Feb; 70(2):

677-87; ISSN: 0022-3042.

UNITED-STATES. Glutamate excitotoxicity is implicated in

several neurodegenerative diseases; consequently,

considerable effort has been made to elucidate

neuroprotective mechanisms against such toxicity. N-Methyl-

D-aspartate (NMDA) receptor desensitisation is one potential

mechanism for controlling glutamate-mediated neuronal cell

death. Pretreatment of rat cerebellar granule cells with

subtoxic concentrations of NMDA caused a marked reduction in

the calcium signals generated by subsequent glutamate

stimulation, and, furthermore, this receptor desensitisation

was coupled to a reduction in glutamate-induced apoptotic-

like death. These effects were reduced by either D-2-amino-5-

phosphonopentanoic acid, an NMDA receptor antagonist, or

cyclosporin A, an inhibitor of calcineurin. Thus, the results

support a role for receptor desensitisation in protection from

glutamate-mediated apoptotic-like neuronal cell death.. EC

3.1.3.-; 0; 0; 0; 0; 56-86-0; 59865-13-3; 6384-92-5; 7440-

70-2; 76726-92-6.

205. Worthington, S.; Arbuckle, S.; Nelson, P.; Carey, W.; Lipson, A.;

Fagan, E. Carbohydrate deficient glycoprotein syndrome type I:

a cause of cerebellar vermis hypoplasia. J-Paediatr-Child-

Health. 1997 Dec; 33(6): 531-4; ISSN: 1034-4810.

AUSTRALIA. To report the first case of carbohydrate deficient

glycoprotein syndrome Type I (CDG I) that has been identified

in Australia and confirmed enzymatically to raise the

awareness of paediatricians with regard to CDG I and its

manifestations, implications and diagnostic investigations.

Clinical and autopsy findings of an infant with CDG I are

presented. The diagnosis of CDG I was suggested by the

clinical findings and biochemical abnormalities and was

confirmed by showing an abnormal transferrin isoform pattern.

Subsequent studies showed a reduced level of

phosphomannomutase in skin fibroblasts. Carbohydrate-

deficient glycoprotein syndrome I is one of the many causes of

cerebellar hypoplasia. It is an important disorder to identify

because of the prognostic and genetic implications and may be

underdiagnosed in Australia.. 11096-37-0.

206. Xi, M. C.; Yamuy, J.; Liu, R. H.; Morales, F. R.; Chase, M. H. Dorsal

spinocerebellar tract neurons are not subjected to

postsynaptic inhibition during carbachol-induced motor

inhibition. J-Neurophysiol. 1997 Jul; 78(1): 137-44; ISSN:

0022-3077.

UNITED-STATES. Dorsal spinocerebellar tract (DSCT) neurons

in Clarke's column in the lumbar spinal cord of cats

anesthetized with alpha-chloralose were recorded

intracellularly. The membrane potential activity and

electrophysiological properties of these neurons were

examined before and during the state of active-sleep-like

motor inhibition induced by the injection of carbachol into the

nucleus pontis oralis. The synaptic activity of DSCT neurons

during carbachol-induced motor inhibition did not change

compared with that during control conditions. In particular,

there was an absence of inhibitory postsynaptic potentials

(IPSPs) in high-gain recordings from DSCT neurons and the

resting membrane potential of DSCT neurons was not

significantly hyperpolarized during carbachol-induced motor

inhibition. The mean amplitude of both monosynaptic

excitatory postsynaptic potentials and disynaptic IPSPs

evoked in DSCT neurons following stimulation of group I

muscle afferents after the injection of carbachol was similar

to that evoked before the injection of carbachol. There were no

significant changes in the mean input resistance and

membrane time constant of DSCT neurons during carbachol-

induced motor inhibition. We conclude that, in contrast to

lumbar motoneurons, DSCT neurons in Clarke's column are not

postsynaptically inhibited during carbachol-induced motor

inhibition. Therefore the population of spinal cord Ib

interneurons that inhibit both DSCT neurons and lumbar

motoneurons is not likely to be the interneurons that are

responsible for the postsynaptic inhibition of motoneurons

that occurs during carbachol-induced motor inhibition. The

present findings also indicate that transmission through the

DSCT is not modulated by postsynaptic inhibition at the level

of DSCT neurons during carbachol-induced motor inhibition.

207. Yamaguchi, K.; Goto, N. Three-dimensional structure of the human

cerebellar dentate nucleus: a computerized reconstruction

study. Anat-Embryol-Berl. 1997 Oct; 196(4): 343-8; ISSN:

0340-2061.

GERMANY. To explore the regional differences in neuronal

cytoarchitecture of human dentate nucleus, we examined first

the three-dimensional structure of this nucleus with a

computerized reconstruction technique, after making serial

sections of the brain in seven fetuses aged from 20 to 39

weeks of gestation (WG), an infant (1-month-old) and two

adults (22- and 85-year-old). The surface was broadly smooth

at 20-22 weeks, but primary gyri or fissures were noticed in

the rostral half of the lateral surface, earliest in its dorsal

region. A small cavity (the hilus nuclei dentati) was situated

in the middle of the medial surface, with four distinct

margins. A great progress in gyration was noted after 22

weeks: gyri were observed over the entire surface by 28-29

weeks. Gyri were thicker in the caudal half than the rostral

half both in the lateral and the medial surfaces. At this stage,

the rostral margin of the hilus was partially cut off and the

hilus was elongated toward the rostral tip, but its relative

size appeared to be grossly equal to that at 22 weeks. The

hilus began to open wider and wider after 30 weeks.

Subdivision of the human dentate nucleus into two different

parts (the smaller microgyric rostral part and the larger

macrogyric caudal part) was accomplished by 35 weeks. We

have previously, using morphometric approaches, reported that

a vulnerable (or critical) period may exist during 20-30 weeks

in the fetal development of the dentate nucleus. It is possible

that this special ten weeks of mid-gestation may be

coincident with the time of extensive growth in gyration for

this nucleus. It will be necessary to sample the neurons

independently from at least two different parts, as described

above, to design further microscopic studies on the regional

differences or on other cytological investigations.

208. Yamamoto, K.; Kobayashi, Y.; Takemura, A.; Kawano, K.; Kawato, M.

A mathematical model that reproduces vertical ocular

following responses from visual stimuli by reproducing the

simple spike firing frequency of Purkinje cells in the

cerebellum. Neurosci-Res. 1997 Oct; 29(2): 161-9; ISSN: 0168-

0102.

IRELAND. A mathematical model that accurately reproduces

eye movements from visual stimuli and incorporates

intermediate neural signals is useful for quantitative analysis

of the neural mechanisms involved in transforming visual

stimuli to eye movements. Here we describe a mathematical

model consisting of two systems: a non-linear system that

relates retinal slip to simple spike firing frequency of

Purkinje cells in the ventral paraflocculus (VPFL) and a linear

system that relates VPFL simple spike firing frequency to eye

movement. This model accurately reproduced the firing

frequency of Purkinje cells and ocular following responses

from visual stimulation paradigms used in physiological

experiments.

209. Yang, G.; Feddersen, R. M.; Zhang, F.; Clark, H. B.; Beitz, A. J.;

Iadecola, C. Cerebellar vascular and synaptic responses in

normal mice and in transgenics with Purkinje cell dysfunction.

Am-J-Physiol. 1998 Feb; 274(2 Pt 2): R529-40; ISSN: 0002-

9513.

UNITED-STATES. We used transgenic mice with Purkinje cell

dysfunction (PO3 line) to study the role of these neurons in the

increase in cerebellar blood flow (BFcrb) produced by

stimulation of the cerebellar parallel fibers (PF). Mice (age 8-

10 wk) were anesthetized (halothane) and artificially

ventilated. Arterial pressure and end-tidal CO2 were

monitored continuously. Arterial blood gases were measured.

The PF were stimulated electrically (100 microA, 30 Hz; 40 s),

and the increases in BFcrb were monitored by a laser-Doppler

flow probe. First, we characterized the increases in BFcrb and

the field potentials produced by PF stimulation in normal mice.

PF stimulation evoked the typical field potentials and

increased BFcrb by 60 +/- 4% (100 microA, 30 Hz; n = 10). The

increases in BFcrb were attenuated by the broad-spectrum

glutamate receptor antagonist kynurenate (-84 +/- 3%; P <

0.05 analysis of variance; n = 5), by the DL-alpha-amino-3-

hydroxy-5-methylisoxazole-4-propionic acid receptor

antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-

benzo(f)quinoxaline (-62 +/- 6%; P < 0.05; n = 5), and by the

nitric oxide synthase inhibitor N omega-nitro-L-arginine (-46

+/- 7%; P < 0.05; n = 5). In PO3 transgenic mice, the increases

in BFcrb produced by PF stimulation were reduced (P < 0.001)

at every stimulus intensity and frequency tested (residual

increase at 100 microA, 30 Hz: 19 +/- 2%; n = 6). The field

potentials evoked by PF stimulation also were abnormal in

that they lacked the late negative wave (n = 6), a finding

consistent with lack of depolarization of Purkinje cells. The

residual flow response in the transgenics was abolished by N

omega-nitro-L-arginine (n = 5; P > 0.05). Ultrastructural

studies showed that the density of PF-Purkinje cell synapses

is reduced in PO3 mice, whereas the morphology of molecular

layer interneurons (stellate cells) is normal. The findings

suggest that Purkinje cells are responsible for a sizable

component of the flow response whereas molecular layer

interneurons mediate the remainder of the response. The study

provides evidence that mouse mutants with spontaneous or

genetically engineered cerebellar abnormalities could be

useful to study the cellular and molecular correlates of

functional hyperemia in the central nervous system.. EC

1.14.13.39; 0; 0; 0; 0; 118876-58-7; 2149-70-4; 492-27-3.

210. Yang, G.; Iadecola, C. Activation of cerebellar climbing fibers

increases cerebellar blood flow: role of glutamate receptors,

nitric oxide, and cGMP. Stroke. 1998 Feb; 29(2): 499-507;

discussion 507-8; ISSN: 0039-2499.

UNITED-STATES. BACKGROUND: The mechanisms regulating the

cerebellar microcirculation during neural activity are poorly

understood. One of the major neural inputs to the cerebellar

cortex is the climbing fiber (CF), a pathway that uses

excitatory amino acids, including glutamate, as a transmitter.

We studied whether CF activation increases cerebellar blood

flow (BFcrb) and, if so, we investigated the role of glutamate

receptors, nitric oxide (NO) and cGMP, in the response.

METHODS: The CF were activated by harmaline administration

(40 mg/kg, i.p.) in halothane-anesthetized rats with a cranial

window placed over the cerebellar vermis. BFcrb was

monitored by a laser-Doppler probe, and arterial pressure and

blood gases were controlled. RESULTS: With Ringer

superfusion, harmaline produced sustained increases in BFcrb

that peaked 20 minutes after administration (+115 +/- 13%;

n=6; P<.05). The increases in BFcrb were substantially reduced

by superfusion with tetrodotoxin (10 micromol/L; -91 +/- 5%;

n=5; P<.05 from Ringer). The response was also attenuated by

the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic

acid (AMPA) receptor inhibitor 2,3-dihydroxy-6-nitro-7-

sulfamoyl-benzo-(F)-quinoxaline (100 micromol/L; -70 +/-

6%; P<.05; n=5), but not by the N-methyl-D-aspartate receptor

blocker 2-amino-5-phosphonopentanoic acid (500 micromol/L;

P>.05; n=5). The response was attenuated by the nonselective

NO synthase (NOS) inhibitor nitro-L-arginine (1 mmol/L; -73

+/- 5%; n=6) or by 7-NI (50 mg, i.p.; -71 +/- 5%; n=5), a

relatively selective neuronal NOS inhibitor. The soluble

guanylyl cyclase inhibitor 1H-1,2,4oxadiazolo[4,3-

a]quinoxalin-1-one (100 micromol/L) attenuated the response

to harmaline (-73 +/- 5; P<.05; n=6) but not to superfusion

with adenosine (P>.05; n=5) or 8-bromo-cGMP (P>.05; n=5).

CONCLUSIONS: Activation of the CF system increases BFcrb.

The response depends on activation of glutamate receptors and

is in large part mediated by NO via stimulation of soluble

guanylyl cyclase. Glutamate receptors NO and cGMP are

important factors in the mechanisms of functional hyperemia

in cerebellar cortex.. 0; 0; 0; 0; 0; 10102-43-9; 118876-58-7;

124-38-9; 2149-70-4; 304-21-2; 31356-94-2; 4368-28-9;

52-67-5; 56-86-0; 7665-99-8; 76726-92-6; 7782-44-7;

79032-48-7.

211. Yew, D. T.; Luo, C. B.; Heizmann, C. W.; Chan, W. Y. Differential

expression of calretinin, calbindin D28K and parvalbumin in

the developing human cerebellum. Brain-Res-Dev-Brain-Res.

1997 Oct 20; 103(1): 37-45; ISSN: 0165-3806.

NETHERLANDS. Three calcium-binding proteins, calretinin,

calbindin D28K and parvalbumin, were immunohistochemically

localized in the human cerebellum at different developmental

stages. Cells positive for calretinin were not detected during

early development of the cerebellum until 21 weeks of

gestation at which stage weak staining was found in Purkinje

and basket cells of the cortex and in neurons of the dentate

nucleus. Both the number of positive cells and the intensity of

immunoreactivities were found to increase as the cerebellum

became more mature. Calbindin D28K immunoreactivity was,

however, detected early in development at 14 weeks of

gestation. Positive cells were found in Purkinje, basket,

stellate and granule cells of the cerebellar cortex and in

neurons of fastigial, globose, emboliform and dentate nuclei.

The number of positive cells and the staining intensity for

calbindin in both the cerebellar cortex and deep nuclei

decreased at more advanced developmental stages. At 21-31

weeks of gestation, positive staining was restricted to

Purkinje and basket cells of the cortex. Parvalbumin

immunoreactivity was also observed early in development at

14 weeks of gestation. Positivity was found in Purkinje,

basket and stellate cells of the cerebellar cortex and in

neurons of all the deep nuclei, with the highest number of

positive cells in the fastigial nucleus followed by emboliform,

globose and dentate nuclei. As the cerebellum became more

mature, both the number of positive cells and the staining

intensity for parvalbumin decreased in the cortex and deep

nuclei. The results of the present study showed that among the

three calcium-binding proteins examined, strong

immunoreactivities for calbindin D28K and parvalbumin were

found inthe human cerebellum early in development at 14

weeks of gestation, but there was a decrease in both the

intensity and number of positive cells at more advanced

stages. In contrast, calretinin positive cells were not detected

until 21 weeks of gestation and the immunoreactivity

increased as the cerebellum became more mature. A possible

correlation between the developmentally regulated expression

of the calcium-binding proteins and expression of different

neurotransmitters during development is discussed.. 0; 0; 0; 0;

0.

212. Yoneshima, H.; Nagata, E.; Matsumoto, M.; Yamada, M.; Nakajima, K.;

Miyata, T.; Ogawa, M.; Mikoshiba, K. A novel neurological mutant

mouse, yotari, which exhibits reeler-like phenotype but

expresses CR-50 antigen/reelin. Neurosci-Res. 1997 Nov;

29(3): 217-23; ISSN: 0168-0102.

IRELAND. We present yotari, a novel neurological mutant

mouse whose mutation is transmitted in an autosomal

recessive manner. The phenotype of yotari is very similar to

that of reeler. yotari mutants are recognizable by their

unstable gait and tremor and by their early deaths at around

the time of weaning. The cerebella of homozygous yotari are

hypoplastic and have no foliation. A molecular and a granular

cell layer can be identified, but Purkinje cells are scattered

throughout both the granular layer and white matter. The

laminar structure of the cerebral cortex and the hippocampal

formation are also distorted. To test whether the mutated

gene in yotari is the reeler gene, reelin, yotari heterozygotes

were mated with reeler homozygotes or heterozygotes. The

absence of abnormal offspring indicated that the yotari gene is

distinct from reelin. Furthermore, expression of mRNA and

protein of reelin was verified by Northern blotting and

immunohistochemistry using a CR-50 monoclonal antibody

(mAb) which is specific to Reelin, the reelin gene product.

Although the mutation of several genes, including cyclin-

dependent kinase 5 (Cdk 5), p35 and LIS1, 45 kDa subunits of

platelet-activating factor acetylhydrolase (PAF-AH) Ib, in

Miller-Dieker lissencephaly syndrome (MDS) has been reported

to cause abnormal laminar structure in the brain, no

abnormality was found in yotari by Western blotting with

antibodies (Ab's) against these molecules. The close similarity

of the phenotypes of yotari and reeler and the expression of

reelin in yotari may suggest that the gene mutated in yotari

encodes a molecule that is on the same signaling pathway as

Reelin, the product of reelin. yotari will provide valuable clues

to explore the molecular mechanism of neuronal migration and

orderly laminar structure formation of the brain.. 0; 0; 0; 0; 0.

213. Yu, K. C.; Arriaga, M. A.; Chen, D. A. Cerebellopontine angle tumor

outcomes in patients with hazardous occupations.

Laryngoscope. 1997 Dec; 107(12 Pt 1): 1610-3; ISSN: 0023-

852X.

UNITED-STATES. Cerebellopontine angle (CPA) tumor surgery

can produce a spectrum of sensory and motor deficits that can

alter a patient's lifestyle and occupation. An important

consideration is whether patients can return to full

occupational status especially when hazardous duties are

involved. Outcome data in CPA tumor surgery usually report

that most patients are able to return to preoperative function;

however, whether these patients can return to hazardous

duties is not specified. A retrospective study of 380

consecutive, operated CPA tumor patients was performed and

37 were identified who engaged in hazardous occupations

including active military service, working at dangerous

heights, piloting jet aircraft, aircraft navigating, and factory

work with high-impact machinery. Overall, patients were able

to resume full-time work in their previous occupations and

86% of patients reported that they were able to resume

hazardous duties. CPA tumor surgery is compatible with

continued full occupational duties after surgery, even for

patients employed in hazardous situations.

214. Yue, Q.; Jen, J. C.; Nelson, S. F.; Baloh, R. W. Progressive ataxia due

to a missense mutation in a calcium-channel gene. Am-J-Hum-

Genet. 1997 Nov; 61(5): 1078-87; ISSN: 0002-9297.

UNITED-STATES. We describe a family with severe

progressive cerebellar ataxia involving the trunk, the

extremities, and speech. The proband, who has prominent

atrophy of the cerebellum, shown by magnetic resonance

imaging, was confined to a wheelchair at the age of 44 years.

Two sons have episodes of vertigo and ataxia that are not

responsive to acetazolamide. Quantitative eye-movement

testing showed a consistent pattern of abnormalities

localizing to the cerebellum. Genotyping suggested linkage to

chromosome 19p, and SSCP showed an aberrant migrating

fragment in exon 6 of the calcium-channel gene CACNA1A,

which cosegregated with the disease. Sequencing of exon 6

identified a G-->A transposition in one allele, at nucleotide

1152, resulting in a predicted glycine-to-arginine substitution

at codon 293. The CAG-repeat expansion associated with

spinocerebellar ataxia 6 was not present in any family

members. This family is unique in having a non-CAG-repeat

mutation that leads to severe progressive ataxia. Since a great

deal is known about the function of calcium channels, we

speculate on how this missense mutation leads to the

combination of clinical symptoms and signs.. 0; 0.

215. Zanata, G. Encephalocele: experimental model. Morphogenesis,

pathogenesis and clinical correlations discussion. J-

Neurosurg-Sci. 1997 Sep; 41(3): 235-48; ISSN: 0390-5616.

ITALY. RESEARCH OBJECT: This study intends to consider an

encephalocele experimental model, obtained in embryonate

eggs, treated in a post-neurulation phase with chemical

teratogens. This study intends to point out possibility that

pathogenic process, which have determined a malformation, is

referable to an original defect of embryonic cranial coatings

development and that neurulation defect is secondary.

EXPERIMENTAL PLAN: Chick and duck embryonate eggs have

been used. They have been inoculated in their development

phase with known chemical teratogens, as Dintoina and Blue

Trypan. A controlling group has been inoculated with

physiological solution and, then, it has been followed till the

hatching. The experimental group has been undergone to

artificial hatching, according to prearranged conditions and it

has been analysed during different phases of its development.

MEASURES: Four cranioencephalic malformations have been

obtained: three cases of encephalocele and one case of

exencephalia. The individual pathological compounds have been

studied under the morphological and histopathological profile.

The skull base dimensions have been taken and then compared

with the controlling group ones. CONCLUSIONS: In the light of

experimental data, some considerations have been undertaken

considering the pathogenetic hypothesis findable in medical

literature, stressing the possibility that encephalocele may be

arranged as a post-neurulation defect and that, for taxonomic

aims, it has to fit in a different group within cranial

disraphims.

216. Zanjani, H. S.; Vogel, M. W.; Martinou, J. C.; Delhaye Bouchaud, N.;

Mariani, J. Postnatal expression of Hu-bcl-2 gene in Lurcher

mutant mice fails to rescue Purkinje cells but protects

inferior olivary neurons from target-related cell death. J-

Neurosci. 1998 Jan 1; 18(1): 319-27; ISSN: 0270-6474.

UNITED-STATES. The Lurcher mutant has been extensively

studied as a model for cell-autonomous and target-related cell

death, yet there are still many unknowns concerning the

mechanisms of neuronal degeneration in this mutant. As a key

regulator of apoptosis, a bcl-2 transgene has been

overexpressed in the heterozygous Lurcher mutant to

investigate the effects of BCL-2 on two types of in vivo

neuronal cell loss in Lurcher: cell-autonomous Purkinje cell

degeneration and target-related olivary neuron death. Six adult

+/Lc mutants expressing a human bcl-2 transgene (Hu-bcl-2)

were generated by crossing +/Lc mutants with NSE71 Hu-bcl-2

transgenic mice. Analysis of these brains showed that bcl-2

overexpression did not prevent +/Lc Purkinje cell

degeneration, but it did rescue most olivary neurons from

target-related cell death. Although the number of olivary

neurons was equivalent to wild-type numbers, the inferior

olive nucleus was significantly shorter in its rostrocaudal

extent, suggesting that olivary neurons are atrophied. We

propose that Lurcher gene action causes Purkinje cell

degeneration independently of a BCL-2-mediated pathway.

Furthermore, although bcl-2 overexpression rescues olivary

neurons from target-related cell death, it does not prevent the

atrophy associated with the loss of target-related trophic

support.. 0.

217. Zona, C.; Ciotti, M. T.; Avoli, M. Topiramate attenuates voltage-

gated sodium currents in rat cerebellar granule cells.

Neurosci-Lett. 1997 Aug 15; 231(3): 123-6; ISSN: 0304-3940.

IRELAND. Whole-cell, voltage-clamp recordings were made

from rat cerebellar granule cells in culture under experimental

conditions designed to study voltage-gated Na+ currents that

were elicited by depolarizing commands from a holding

potential of -60 mV up to +20 mV. These tetrodotoxin-

sensitive inward currents were reduced in a dose-related

manner by bath application of the structurally novel,

anticonvulsant drug topiramate (10-1000 microM; n = 16).

Dose-response analysis of this effect revealed an IC50 of 48.9

microM. Topiramate also made the steady-state inactivation

curve of this current shift toward more negative values

(midpoint of the inactivation curve -46.9 mV under control

conditions and -56.5 mV during topiramate application; n = 5).

We propose that these effects may contribute to control the

sustained depolarizations with repetitive firing of action

potentials that occur within neuronal networks during seizure

activity. Therefore they may represent a mechanism of action

for this novel anticonvulsant drug.. 0; 0; 30237-26-4; 4368-

28-9; 7440-23-5; 97240-79-4.