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