280. Liu, N. J.; Bao, H.; Li, N.; Yu, Y. X.; Han, J. S. Cholecystokinin

octapeptide reverses the inhibitory effect induced by

electroacupuncture on C-fiber evoked discharges. Int-J-

Neurosci. 1996 Sep; 86(3-4): 241-7; ISSN: 0020-7454.

ENGLAND. Extracellular single unit recordings were made from

spinal dorsal horn wide dynamic range neurons in spinal

transected, urethane-anesthetized rats. The unit discharges

elicited by noxious electrical stimulation of the hind paw

were suppressed by electroacupuncture (15 Hz, 0.3 ms, 3 mA,

30 min) placed at the hind leg points (S-36 and SP-6). Local

spinal superfusion with naloxone (20 micrograms/15

microliters) or CCK-8 (10 ng/15 microliters) attenuated,

whereas CCK-B receptor antagonist L365,260 (2.5

micrograms/15 microliters) enhanced the electroacupuncture

effect. These findings provide further evidence for the notion

that CCK-8, in the spinal cord, functions as an antiopioid

substrate that antagonizes opioid- or electroacupuncture-

induced analgesia.. 25126-32-3.

281. Liu, R. H.; Bertolotto, C.; Engelhardt, J. K.; Chase, M. H. Age-related

changes in soma size of neurons in the spinal cord motor

column of the cat. Neurosci-Lett. 1996 Jun 28; 211(3): 163-6;

ISSN: 0304-3940.

IRELAND. The present study was undertaken to examine the

effect of the aging process on the soma size and number of

motoneurons and interneurons in the motor column of the

spinal cord of old cats. Neurons in the motor column were

divided into small and large populations based on a bimodal

distribution of their soma cross-sectional areas. A 17%

decrease in the cross-sectional area of small neurons was

observed, this decrease was statistically significant (P <

0.0001). The cross-sectional area of large neurons decreased

by only 6%, which was statistically significant (P < 0.05). On

the other hand, there was no significant difference in the

number of large, small or of these combined population of

ventral horn neurons in the aged cats compared with the

control animals. This data suggest that neurons in the motor

column are not uniformly affected by the aging process

because morphological changes are proportionally greater in

small neurons than in large neurons.

282. Liu, R. H.; Bertolotto, C.; Engelhardt, J. K.; Chase, M. H. Age-related

changes in soma size of neurons in the spinal cord motor

column of the cat. Neurosci-Lett. 1996 Jun 28; 211(3): 163-6;

ISSN: 0304-3940.

IRELAND. The present study was undertaken to examine the

effect of the aging process on the soma size and number of

motoneurons and interneurons in the motor column of the

spinal cord of old cats. Neurons in the motor column were

divided into small and large populations based on a bimodal

distribution of their soma cross-sectional areas. A 17%

decrease in the cross-sectional area of small neurons was

observed, this decrease was statistically significant (P <

0.0001). The cross-sectional area of large neurons decreased

by only 6%, which was statistically significant (P < 0.05). On

the other hand, there was no significant difference in the

number of large, small or of these combined population of

ventral horn neurons in the aged cats compared with the

control animals. This data suggest that neurons in the motor

column are not uniformly affected by the aging process

because morphological changes are proportionally greater in

small neurons than in large neurons.

283. Logan, S. D.; Pickering, A. E.; Gibson, I. C.; Nolan, M. F.; Spanswick,

D. Electrotonic coupling between rat sympathetic

preganglionic neurones in vitro. J-Physiol-Lond. 1996 Sep 1;

495( Pt 2): 491-502; ISSN: 0022-3751.

ENGLAND. 1. Using the whole-cell recording technique in rat

spinal cord slices we have shown that 26% of sympathetic

preganglionic neurones (SPNs) show spontaneous membrane

potential oscillations. These oscillations consist of trains of

biphasic waves, which we have termed spikelets because of

their similarity to truncated action potentials. 2. The

spikelets were inhibited by TTX and anaesthetics such as

alpha-chloralose but not by the intracellular application of

lidocaine N-ethyl bromide (QX-314). 3. By stimulating the

ventral roots we have demonstrated the presence of short-

latency depolarizations (SLDs) in oscillating neurones. These

SLDs have a similar waveform to the spontaneous spikelets,

and also show the ability to override the frequency of

occurrence of the spontaneous spikelets. These observations

suggest that the spikelets result from electrotonic coupling

between the oscillating SPNs. 4. SLDs were also observed in a

population of non-oscillating, electrotonically coupled,

quiescent SPNs. It was possible to induce oscillations in these

neurones by the injection of depolarizing current (in the

presence of QX-314), suggesting that these neurones are also

gap-junction coupled. 5. Simultaneous whole-cell recordings

were obtained from twenty-three pairs of SPNs. Two pairs

displayed both spontaneous, synchronized oscillations and

action potentials. Electrotonic coupling was confirmed by the

detection of membrane polarization in both neurones in

response to current injected into one neurone. In a further two

pairs of quiescent SPNs, injection of depolarizing current

pulses into one neurone induced action potential discharge in

that neurone and a depolarization and oscillations in the other

neurone. 6. The ability of groups of electrotonically coupled

SPNs to generate spontaneous discharges within the spinal

cord provides a novel mechanism for the integration and

synchronization of information within the sympathetic

nervous system.. 0; 137-58-6; 21306-56-9; 4368-28-9;

7440-70-2.

284. Logan, S. D.; Pickering, A. E.; Gibson, I. C.; Nolan, M. F.; Spanswick,

D. Electrotonic coupling between rat sympathetic

preganglionic neurones in vitro. J-Physiol-Lond. 1996 Sep 1;

495( Pt 2): 491-502; ISSN: 0022-3751.

ENGLAND. 1. Using the whole-cell recording technique in rat

spinal cord slices we have shown that 26% of sympathetic

preganglionic neurones (SPNs) show spontaneous membrane

potential oscillations. These oscillations consist of trains of

biphasic waves, which we have termed spikelets because of

their similarity to truncated action potentials. 2. The

spikelets were inhibited by TTX and anaesthetics such as

alpha-chloralose but not by the intracellular application of

lidocaine N-ethyl bromide (QX-314). 3. By stimulating the

ventral roots we have demonstrated the presence of short-

latency depolarizations (SLDs) in oscillating neurones. These

SLDs have a similar waveform to the spontaneous spikelets,

and also show the ability to override the frequency of

occurrence of the spontaneous spikelets. These observations

suggest that the spikelets result from electrotonic coupling

between the oscillating SPNs. 4. SLDs were also observed in a

population of non-oscillating, electrotonically coupled,

quiescent SPNs. It was possible to induce oscillations in these

neurones by the injection of depolarizing current (in the

presence of QX-314), suggesting that these neurones are also

gap-junction coupled. 5. Simultaneous whole-cell recordings

were obtained from twenty-three pairs of SPNs. Two pairs

displayed both spontaneous, synchronized oscillations and

action potentials. Electrotonic coupling was confirmed by the

detection of membrane polarization in both neurones in

response to current injected into one neurone. In a further two

pairs of quiescent SPNs, injection of depolarizing current

pulses into one neurone induced action potential discharge in

that neurone and a depolarization and oscillations in the other

neurone. 6. The ability of groups of electrotonically coupled

SPNs to generate spontaneous discharges within the spinal

cord provides a novel mechanism for the integration and

synchronization of information within the sympathetic

nervous system.. 0; 137-58-6; 21306-56-9; 4368-28-9;

7440-70-2.

285. Lu, J.; Ebraheim, N. A.; Biyani, A.; Brown, J. A.; Yeasting, R. A.

Vulnerability of great medullary artery. Spine. 1996 Aug 15;

21(16): 1852-5; ISSN: 0362-2436.

UNITED-STATES. STUDY DESIGN: The present study describes

anatomic observations on great medullary artery and

intercostal arteries pertinent to thoracolumbar spinal surgery.

OBJECTIVES: This study reveals the vulnerable course of the

great medullary artery and its relationship to the lateral or

posterolateral approach to thoracic spine. SUMMARY OF

BACKGROUND DATA: There are no previous anatomic data on the

length of the great medullary artery, its intradural course, its

relationship with the anterior spinal artery, and the distance

between two adjacent intercostal arteries. METHODS: The

location of the intercostal arteries was defined, and the

distance between two adjacent arteries was measured at a

point on the lateral surface of the vertebra midway between

its anteroposterior diameter. The intradural length of the

great medullary artery and the angle it formed with the

anterior spinal artery at the point of anastomosis were also

measured. RESULTS: The mean intradural length of the great

medullary artery was 3.6 cm (range, 1.7-8.1 cm), and it passed

over 1-3 disc spaces before joining the anterior spinal artery

at a mean angle of 20.1 degrees (range, 12-28 degrees). The

average distance between two adjacent intercostal arteries

from T6 to L2 was 3.6 cm (range, 2.8-4.0 cm), which provides

a safe window through which a herniated thoracic disc may be

approached if surgery is indicated. CONCLUSIONS: The acute

angle between the great medullary artery and anterior spinal

artery indicates that these two arteries are in close proximity

for considerable length and are liable to be compressed

together with the intervening vascular collaterals by a space-

occupying lesion, such as disc herniation or a fractured

fragment. The longer the intradural course of the great

medullary artery, the more vulnerable it is to compression by

disc herniation or fracture. The intercostal and lumbar

arteries are located at the midportion of the lateral aspect of

the vertebral bodies rather than at the level of intervertebral

discs. Discectomy or decompression of the anterior thoracic

canal may be accomplished through a lateral or posterolateral

extracavitary approach between two intercostal or lumbar

arteries.

286. Lu, J.; Ebraheim, N. A.; Biyani, A.; Brown, J. A.; Yeasting, R. A.

Vulnerability of great medullary artery. Spine. 1996 Aug 15;

21(16): 1852-5; ISSN: 0362-2436.

UNITED-STATES. STUDY DESIGN: The present study describes

anatomic observations on great medullary artery and

intercostal arteries pertinent to thoracolumbar spinal surgery.

OBJECTIVES: This study reveals the vulnerable course of the

great medullary artery and its relationship to the lateral or

posterolateral approach to thoracic spine. SUMMARY OF

BACKGROUND DATA: There are no previous anatomic data on the

length of the great medullary artery, its intradural course, its

relationship with the anterior spinal artery, and the distance

between two adjacent intercostal arteries. METHODS: The

location of the intercostal arteries was defined, and the

distance between two adjacent arteries was measured at a

point on the lateral surface of the vertebra midway between

its anteroposterior diameter. The intradural length of the

great medullary artery and the angle it formed with the

anterior spinal artery at the point of anastomosis were also

measured. RESULTS: The mean intradural length of the great

medullary artery was 3.6 cm (range, 1.7-8.1 cm), and it passed

over 1-3 disc spaces before joining the anterior spinal artery

at a mean angle of 20.1 degrees (range, 12-28 degrees). The

average distance between two adjacent intercostal arteries

from T6 to L2 was 3.6 cm (range, 2.8-4.0 cm), which provides

a safe window through which a herniated thoracic disc may be

approached if surgery is indicated. CONCLUSIONS: The acute

angle between the great medullary artery and anterior spinal

artery indicates that these two arteries are in close proximity

for considerable length and are liable to be compressed

together with the intervening vascular collaterals by a space-

occupying lesion, such as disc herniation or a fractured

fragment. The longer the intradural course of the great

medullary artery, the more vulnerable it is to compression by

disc herniation or fracture. The intercostal and lumbar

arteries are located at the midportion of the lateral aspect of

the vertebral bodies rather than at the level of intervertebral

discs. Discectomy or decompression of the anterior thoracic

canal may be accomplished through a lateral or posterolateral

extracavitary approach between two intercostal or lumbar

arteries.

287. Lubischer, J. L.; Arnold, A. P. Axotomy transiently down-regulates

androgen receptors in motoneurons of the spinal nucleus of the

bulbocavernosus. Brain-Res. 1995 Oct 2; 694(1-2): 61-8; ISSN:

0006-8993.

NETHERLANDS. Testosterone is an important trophic factor for

motoneurons in the spinal nucleus of the bulbocavernosus

(SNB), and SNB motoneurons are more responsive to

testosterone than are other motoneurons. Axonal injury during

early postnatal life prevents the normal development of

steroid-sensitivity by adult SNB motoneurons. Axonal injury

also causes changes in the expression by motoneurons of a

wide range of proteins, including the up-regulation of trophic

factor receptors. We have used a polyclonal antibody (PG-21;

G.S. Prins) to study the expression of androgen receptors in

SNB motoneurons after axonal injury. PG-21 labeled

motoneuronal nuclei in the lower lumbar spinal cord of rats in

a pattern that matched autoradiographic reports of androgen

accumulation in this region of the nervous system. A

population of numerous, small cells located dorsal to the

central canal also showed evidence of androgen receptor

expression. Cutting the axons of SNB motoneurons in adulthood

or in development caused a decrease in androgen receptor

immunoreactivity in SNB motoneurons. This is the first report

that a trophic factor receptor in motoneurons is down-

regulated after axonal injury, and is interesting in light of

reports that testosterone treatment can facilitate

motoneuronal regeneration after nerve cut. Androgen receptor

levels subsequently returned to normal, regardless of the age

at axotomy, providing no evidence for a lasting effect of

developmental axotomy on androgen receptor levels in SNB

motoneurons. Thus, axotomy-induced down-regulation of

androgen receptors does not underlie the inability of SNB

motoneurons to respond to androgen treatment several months

after pudendal nerve cut in development.. 0.

288. Lubischer, J. L.; Arnold, A. P. Axotomy transiently down-regulates

androgen receptors in motoneurons of the spinal nucleus of the

bulbocavernosus. Brain-Res. 1995 Oct 2; 694(1-2): 61-8; ISSN:

0006-8993.

NETHERLANDS. Testosterone is an important trophic factor for

motoneurons in the spinal nucleus of the bulbocavernosus

(SNB), and SNB motoneurons are more responsive to

testosterone than are other motoneurons. Axonal injury during

early postnatal life prevents the normal development of

steroid-sensitivity by adult SNB motoneurons. Axonal injury

also causes changes in the expression by motoneurons of a

wide range of proteins, including the up-regulation of trophic

factor receptors. We have used a polyclonal antibody (PG-21;

G.S. Prins) to study the expression of androgen receptors in

SNB motoneurons after axonal injury. PG-21 labeled

motoneuronal nuclei in the lower lumbar spinal cord of rats in

a pattern that matched autoradiographic reports of androgen

accumulation in this region of the nervous system. A

population of numerous, small cells located dorsal to the

central canal also showed evidence of androgen receptor

expression. Cutting the axons of SNB motoneurons in adulthood

or in development caused a decrease in androgen receptor

immunoreactivity in SNB motoneurons. This is the first report

that a trophic factor receptor in motoneurons is down-

regulated after axonal injury, and is interesting in light of

reports that testosterone treatment can facilitate

motoneuronal regeneration after nerve cut. Androgen receptor

levels subsequently returned to normal, regardless of the age

at axotomy, providing no evidence for a lasting effect of

developmental axotomy on androgen receptor levels in SNB

motoneurons. Thus, axotomy-induced down-regulation of

androgen receptors does not underlie the inability of SNB

motoneurons to respond to androgen treatment several months

after pudendal nerve cut in development.. 0.

289. Lukashin, A. V.; Amirikian, B. R.; Georgopoulos, A. P. Neural

computations underlying the exertion of force: a model. Biol-

Cybern. 1996 May; 74(5): 469-78; ISSN: 0340-1200.

GERMANY. We have developed a model that simulates possible

mechanisms by which supraspinal neuronal signals coding

forces could converge in the spinal cord and provide an ongoing

integrated signal to the motoneuronal pools whose activation

results in the exertion of force. The model consists of a three-

layered neural network connected to a two-joint-six-muscle

model of the arm. The network layers represent supraspinal

populations, spinal cord interneurons, and motoneuronal pools.

We propose an approach to train the network so that, after the

synaptic connections between the layers are adjusted, the

performance of the model is consistent with experimental

data obtained on different organisms using different

experimental paradigms: the stiffness characteristics of

human arm; the structure of force fields generated by the

stimulation of the frog's spinal cord; and a correlation

between motor cortical activity and force exerted by monkey

against an immovable object. The model predicts a specific

pattern of connections between supraspinal populations coding

forces and spinal cord interneurons: the weight of connection

should be correlated with directional preference of

interconnected units. Finally, our simulations demonstrate

that the force generated by the sum of neural signals can be

nearly equal to the vector sum of forces generated by each

signal independently, in spite of the complex nonlinearities

intervening between supraspinal commands and forces exerted

by the arm in response to these commands.

290. Lukashin, A. V.; Amirikian, B. R.; Georgopoulos, A. P. Neural

computations underlying the exertion of force: a model. Biol-

Cybern. 1996 May; 74(5): 469-78; ISSN: 0340-1200.

GERMANY. We have developed a model that simulates possible

mechanisms by which supraspinal neuronal signals coding

forces could converge in the spinal cord and provide an ongoing

integrated signal to the motoneuronal pools whose activation

results in the exertion of force. The model consists of a three-

layered neural network connected to a two-joint-six-muscle

model of the arm. The network layers represent supraspinal

populations, spinal cord interneurons, and motoneuronal pools.

We propose an approach to train the network so that, after the

synaptic connections between the layers are adjusted, the

performance of the model is consistent with experimental

data obtained on different organisms using different

experimental paradigms: the stiffness characteristics of

human arm; the structure of force fields generated by the

stimulation of the frog's spinal cord; and a correlation

between motor cortical activity and force exerted by monkey

against an immovable object. The model predicts a specific

pattern of connections between supraspinal populations coding

forces and spinal cord interneurons: the weight of connection

should be correlated with directional preference of

interconnected units. Finally, our simulations demonstrate

that the force generated by the sum of neural signals can be

nearly equal to the vector sum of forces generated by each

signal independently, in spite of the complex nonlinearities

intervening between supraspinal commands and forces exerted

by the arm in response to these commands.

291. Lumsden, A.; Krumlauf, R. Patterning the vertebrate neuraxis.

Science. 1996 Nov 15; 274(5290): 1109-15; ISSN: 0036-8075.

UNITED-STATES. Neuraxial patterning is a continuous process

that extends over a protracted period of development. During

gastrulation a crude anteroposterior pattern, detectable by

molecular markers, is conferred on the neuroectoderm by

signals from the endomesoderm that are largely inseparable

from those of neural induction itself. This coarse-grained

pattern is subsequently reinforced and refined by diverse,

locally acting mechanisms. Segmentation and long-range

signaling from organizing centers are prominent among the

emerging principles governing regional pattern.. 302-79-4.

292. Lumsden, A.; Krumlauf, R. Patterning the vertebrate neuraxis.

Science. 1996 Nov 15; 274(5290): 1109-15; ISSN: 0036-8075.

UNITED-STATES. Neuraxial patterning is a continuous process

that extends over a protracted period of development. During

gastrulation a crude anteroposterior pattern, detectable by

molecular markers, is conferred on the neuroectoderm by

signals from the endomesoderm that are largely inseparable

from those of neural induction itself. This coarse-grained

pattern is subsequently reinforced and refined by diverse,

locally acting mechanisms. Segmentation and long-range

signaling from organizing centers are prominent among the

emerging principles governing regional pattern.. 302-79-4.

293. Luo, L.; Wiesenfeld Hallin, Z. Differential effects of pre-

treatment with intrathecal or intravenous morphine on the

prevention of spinal cord hyperexcitability following sciatic

nerve section in the rat. Acta-Anaesthesiol-Scand. 1996 Jan;

40(1): 91-5; ISSN: 0001-5172.

DENMARK. The effect of intrathecal (i.t.) and intravenous (i.v.)

morphine on spinal hyperexcitability following unilateral

section of the sciatic nerve was studied in decerebrate,

spinalized, unanesthetized rats. Sciatic nerve section evoked a

biphasic, prolonged hyperexcitability of the flexor reflex.

Either i.v. (0.2, 1 or 10 mg center dot kg-1) or i.t. (3 or 10 mu

g) morphine was administered prior to sciatic nerve section.

All doses of morphine significantly depressed the baseline

flexor reflex and abolished the less intense prolonged second

component of reflex hyperexcitability. One and 10, but not 0.2,

mg center dot kg-1 i.v. morphine significantly depressed the

first phase of spinal cord sensitization. However, both 3 mu g

and 10 mu g i.t. morphine were significantly more effective

than i.v. morphine in suppressing spinal cord hyperexcitability.

The present results suggest that moderate doses of i.t.

morphine decrease spinal hyperexcitability following nerve

transection more than even extremely large i.v. doses. The

poorer effect of i.v. morphine on preventing spinal

hyperexcitability may be due to low spinal concentration after

systemic administration.. 0; 57-27-2.

294. Luo, L.; Wiesenfeld Hallin, Z. Differential effects of pre-

treatment with intrathecal or intravenous morphine on the

prevention of spinal cord hyperexcitability following sciatic

nerve section in the rat. Acta-Anaesthesiol-Scand. 1996 Jan;

40(1): 91-5; ISSN: 0001-5172.

DENMARK. The effect of intrathecal (i.t.) and intravenous (i.v.)

morphine on spinal hyperexcitability following unilateral

section of the sciatic nerve was studied in decerebrate,

spinalized, unanesthetized rats. Sciatic nerve section evoked a

biphasic, prolonged hyperexcitability of the flexor reflex.

Either i.v. (0.2, 1 or 10 mg center dot kg-1) or i.t. (3 or 10 mu

g) morphine was administered prior to sciatic nerve section.

All doses of morphine significantly depressed the baseline

flexor reflex and abolished the less intense prolonged second

component of reflex hyperexcitability. One and 10, but not 0.2,

mg center dot kg-1 i.v. morphine significantly depressed the

first phase of spinal cord sensitization. However, both 3 mu g

and 10 mu g i.t. morphine were significantly more effective

than i.v. morphine in suppressing spinal cord hyperexcitability.

The present results suggest that moderate doses of i.t.

morphine decrease spinal hyperexcitability following nerve

transection more than even extremely large i.v. doses. The

poorer effect of i.v. morphine on preventing spinal

hyperexcitability may be due to low spinal concentration after

systemic administration.. 0; 57-27-2.

295. Mannion, R. J.; Doubell, T. P.; Coggeshall, R. E.; Woolf, C. J.

Collateral sprouting of uninjured primary afferent A-fibers

into the superficial dorsal horn of the adult rat spinal cord

after topical capsaicin treatment to the sciatic nerve. J-

Neurosci. 1996 Aug 15; 16(16): 5189-95; ISSN: 0270-6474.

UNITED-STATES. That terminals of uninjured primary sensory

neurons terminating in the dorsal horn of the spinal cord can

collaterally sprout was first suggested by Liu and Chambers

(1958), but this has since been disputed. Recently, horseradish

peroxidase conjugated to the B subunit of cholera toxin (B-

HRP) and intracellular HRP injections have shown that sciatic

nerve section or crush produces a long-lasting rearrangement

in the organization of primary afferent central terminals, with

A-fibers sprouting into lamina II, a region that normally

receives only C-fiber input (Woolf et al., 1992). The

mechanism of this A-fiber sprouting has been thought to

involve injury-induced C-fiber transganglionic degeneration

combined with myelinated A-fibers being conditioned into a

regenerative growth state. In this study, we ask whether C-

fiber degeneration and A-fiber conditioning are both necessary

for the sprouting of A-fibers into lamina II. Local application

of the C-fiber-specific neurotoxin capsaicin to the sciatic

nerve has previously been shown to result in C-fiber damage

and degenerative atrophy in lamina II. We have used B-HRP to

transganglionically label A-fiber central terminals and have

shown that 2 weeks after topical capsaicin treatment to the

sciatic nerve, the pattern of B-HRP staining in the dorsal horn

is indistinguishable from that seen after axotomy, with lamina

II displaying novel staining in the identical region containing

capsaicin-treated C-fiber central terminals. These results

suggest that after C-fiber injury, uninjured A-fiber central

terminals can collaterally sprout into lamina II of the dorsal

horn. This phenomenon may help to explain the pain associated

with C-fiber neuropathy.. EC 1.11.1.-; EC 3.1.3; EC 3.1.3.-; 0;

404-86-4; 9012-63-9.

296. Mannion, R. J.; Doubell, T. P.; Coggeshall, R. E.; Woolf, C. J.

Collateral sprouting of uninjured primary afferent A-fibers

into the superficial dorsal horn of the adult rat spinal cord

after topical capsaicin treatment to the sciatic nerve. J-

Neurosci. 1996 Aug 15; 16(16): 5189-95; ISSN: 0270-6474.

UNITED-STATES. That terminals of uninjured primary sensory

neurons terminating in the dorsal horn of the spinal cord can

collaterally sprout was first suggested by Liu and Chambers

(1958), but this has since been disputed. Recently, horseradish

peroxidase conjugated to the B subunit of cholera toxin (B-

HRP) and intracellular HRP injections have shown that sciatic

nerve section or crush produces a long-lasting rearrangement

in the organization of primary afferent central terminals, with

A-fibers sprouting into lamina II, a region that normally

receives only C-fiber input (Woolf et al., 1992). The

mechanism of this A-fiber sprouting has been thought to

involve injury-induced C-fiber transganglionic degeneration

combined with myelinated A-fibers being conditioned into a

regenerative growth state. In this study, we ask whether C-

fiber degeneration and A-fiber conditioning are both necessary

for the sprouting of A-fibers into lamina II. Local application

of the C-fiber-specific neurotoxin capsaicin to the sciatic

nerve has previously been shown to result in C-fiber damage

and degenerative atrophy in lamina II. We have used B-HRP to

transganglionically label A-fiber central terminals and have

shown that 2 weeks after topical capsaicin treatment to the

sciatic nerve, the pattern of B-HRP staining in the dorsal horn

is indistinguishable from that seen after axotomy, with lamina

II displaying novel staining in the identical region containing

capsaicin-treated C-fiber central terminals. These results

suggest that after C-fiber injury, uninjured A-fiber central

terminals can collaterally sprout into lamina II of the dorsal

horn. This phenomenon may help to explain the pain associated

with C-fiber neuropathy.. EC 1.11.1.-; EC 3.1.3; EC 3.1.3.-; 0;

404-86-4; 9012-63-9.

297. Mansikka, H.; Idanpaan Heikkila, J. J.; Pertovaara, A. Different

roles of alpha 2-adrenoceptors of the medulla versus the

spinal cord in modulation of mustard oil-induced central

hyperalgesia in rats. Eur-J-Pharmacol. 1996 Feb 15; 297(1-2):

19-26; ISSN: 0014-2999.

NETHERLANDS. We attempted to determine the roles of spinal

versus medullary alpha 2-adrenoceptors in modulation of

central hyperalgesia in rats. Central hyperalgesia was

produced by applying mustard oil (50%) to the skin of the ankle

of one hindpaw. The threshold for eliciting a hindlimb flexion

reflex was determined by applying a series of calibrated

monofilaments to the glabrous skin of the hindpaw

contralaterally (= control) or ipsilaterally to the mustard oil-

treated ankle (= outside the area of primary hyperalgesia).

Medetomidine (an alpha 2-adrenoceptor agonist; 1

micrograms), atipamezole (an alpha 2-adrenoceptor

antagonist; 2.5 micrograms) or saline was microinjected into

the lateral reticular nucleus of the medulla, the nucleus raphe

magnus, or intrathecally to the lumbar spinal cord 12 min

before the mustard oil treatment. Following saline injections,

mustard oil produced a significant decrease of the hindlimb

withdrawal threshold in the mustard oil-treated limb but not

in the contralateral limb. Atipamezole in the lateral reticular

nucleus produced a complete reversal of the hyperalgesia but

no effect on the threshold of the intact limb. However,

atipamezole in the raphe magnus nucleus or in the lumbar

spinal cord did not produce a significant attenuation of the

hyperalgesia. Medetomidine in the spinal cord, but not in the

lateral reticular nucleus, reversed the hyperalgesia. At this

dose range (up to 3 micrograms), medetomidine in the spinal

cord of nonhyperalgesic control rats did not produce any

significant change in the withdrawal response of hindlimbs or

in the tail-flick latency. The results indicate that neurogenic

inflammation induces significant plastic changes in the

function of alpha 2-adrenergic pain regulatory mechanisms. In

rats with mustard oil-induced central hyperalgesia, an alpha

2-adrenoceptor antagonist produces an antihyperalgesic effect

due to an action on the caudal ventrolateral medulla, whereas

an alpha 2-adrenoceptor agonist produces an enhanced

antinociceptive effect due to a direct action on the spinal

cord.. 0; 0; 0; 0; 0; 0; 104054-27-5; 8007-40-7; 86347-14-0.

298. Mansikka, H.; Idanpaan Heikkila, J. J.; Pertovaara, A. Different

roles of alpha 2-adrenoceptors of the medulla versus the

spinal cord in modulation of mustard oil-induced central

hyperalgesia in rats. Eur-J-Pharmacol. 1996 Feb 15; 297(1-2):

19-26; ISSN: 0014-2999.

NETHERLANDS. We attempted to determine the roles of spinal

versus medullary alpha 2-adrenoceptors in modulation of

central hyperalgesia in rats. Central hyperalgesia was

produced by applying mustard oil (50%) to the skin of the ankle

of one hindpaw. The threshold for eliciting a hindlimb flexion

reflex was determined by applying a series of calibrated

monofilaments to the glabrous skin of the hindpaw

contralaterally (= control) or ipsilaterally to the mustard oil-

treated ankle (= outside the area of primary hyperalgesia).

Medetomidine (an alpha 2-adrenoceptor agonist; 1

micrograms), atipamezole (an alpha 2-adrenoceptor

antagonist; 2.5 micrograms) or saline was microinjected into

the lateral reticular nucleus of the medulla, the nucleus raphe

magnus, or intrathecally to the lumbar spinal cord 12 min

before the mustard oil treatment. Following saline injections,

mustard oil produced a significant decrease of the hindlimb

withdrawal threshold in the mustard oil-treated limb but not

in the contralateral limb. Atipamezole in the lateral reticular

nucleus produced a complete reversal of the hyperalgesia but

no effect on the threshold of the intact limb. However,

atipamezole in the raphe magnus nucleus or in the lumbar

spinal cord did not produce a significant attenuation of the

hyperalgesia. Medetomidine in the spinal cord, but not in the

lateral reticular nucleus, reversed the hyperalgesia. At this

dose range (up to 3 micrograms), medetomidine in the spinal

cord of nonhyperalgesic control rats did not produce any

significant change in the withdrawal response of hindlimbs or

in the tail-flick latency. The results indicate that neurogenic

inflammation induces significant plastic changes in the

function of alpha 2-adrenergic pain regulatory mechanisms. In

rats with mustard oil-induced central hyperalgesia, an alpha

2-adrenoceptor antagonist produces an antihyperalgesic effect

due to an action on the caudal ventrolateral medulla, whereas

an alpha 2-adrenoceptor agonist produces an enhanced

antinociceptive effect due to a direct action on the spinal

cord.. 0; 0; 0; 0; 0; 0; 104054-27-5; 8007-40-7; 86347-14-0.

299. Marin, O.; Smeets, W. J.; Gonzalez, A. Do amphibians have a true

locus coeruleus? Neuroreport. 1996 May 31; 7(8): 1447-51;

ISSN: 0959-4965.

ENGLAND. Much controversy surrounds the identity of a locus

coeruleus in amphibians because although previous studies on

the isthmic region of the brain of anurans and urodeles

revealed the presence of noradrenergic cell bodies they failed

to demonstrate their projection to the telencephalon or the

spinal cord. In the present study applications of Texas Red-

conjugated dextran amines to the basal telencephalon or to the

spinal cord in combination with tyrosine hydroxylase

immunohistochemistry revealed that the noradrenergic cell

bodies in the isthmic region of anuran (Rana perezi) and

urodele (Pleurodeles waltl) amphibians project to the

telencephalon as well as to the spinal cord. On the basis of

location, neurotransmitter content and efferent projections,

the isthmic noradrenergic cell group of amphibians is,

therefore, considered homologous to the locus coeruleus of

amniotes.

300. Marin, O.; Smeets, W. J.; Gonzalez, A. Do amphibians have a true

locus coeruleus? Neuroreport. 1996 May 31; 7(8): 1447-51;

ISSN: 0959-4965.

ENGLAND. Much controversy surrounds the identity of a locus

coeruleus in amphibians because although previous studies on

the isthmic region of the brain of anurans and urodeles

revealed the presence of noradrenergic cell bodies they failed

to demonstrate their projection to the telencephalon or the

spinal cord. In the present study applications of Texas Red-

conjugated dextran amines to the basal telencephalon or to the

spinal cord in combination with tyrosine hydroxylase

immunohistochemistry revealed that the noradrenergic cell

bodies in the isthmic region of anuran (Rana perezi) and

urodele (Pleurodeles waltl) amphibians project to the

telencephalon as well as to the spinal cord. On the basis of

location, neurotransmitter content and efferent projections,

the isthmic noradrenergic cell group of amphibians is,

therefore, considered homologous to the locus coeruleus of

amniotes.

301. Marsh, A. E.; Barr, B. C.; Madigan, J.; Lakritz, J.; Nordhausen, R.;

Conrad, P. A. Neosporosis as a cause of equine protozoal

myeloencephalitis. J-Am-Vet-Med-Assoc. 1996 Dec 1;

209(11): 1907-13; ISSN: 0003-1488.

UNITED-STATES. Neosporosis was diagnosed in an 11-year-old

Quarter Horse gelding with clinical signs and diagnostic test

results compatible with equine protozoal myeloencephalitis

(EPM). Presumptive postmortem diagnosis of EPM attributable

to Sarcocystis neurona infection is generally made on the

basis of detecting an antibody titer to S neurona in the CSF or

characteristic histologic lesions, even when parasites have

not been specifically identified. Neosporosis was confirmed in

the horse described here by use of immunohistochemical

examination, in vitro culturing, and ultrastructural and

molecular characterization of parasites from infected tissues.

Antibody testing of serum and CSF samples indicated that

Neospora-specific anti-bodies can react with S neurona

proteins on western blot analysis. The confirmation that

neosporosis in horses can mimic EPM emphasizes the need to

broaden the etiologic definition of EPM beyond infections

exclusively attributable to S neurona.. 0; 0.

302. Marsh, A. E.; Barr, B. C.; Madigan, J.; Lakritz, J.; Nordhausen, R.;

Conrad, P. A. Neosporosis as a cause of equine protozoal

myeloencephalitis. J-Am-Vet-Med-Assoc. 1996 Dec 1;

209(11): 1907-13; ISSN: 0003-1488.

UNITED-STATES. Neosporosis was diagnosed in an 11-year-old

Quarter Horse gelding with clinical signs and diagnostic test

results compatible with equine protozoal myeloencephalitis

(EPM). Presumptive postmortem diagnosis of EPM attributable

to Sarcocystis neurona infection is generally made on the

basis of detecting an antibody titer to S neurona in the CSF or

characteristic histologic lesions, even when parasites have

not been specifically identified. Neosporosis was confirmed in

the horse described here by use of immunohistochemical

examination, in vitro culturing, and ultrastructural and

molecular characterization of parasites from infected tissues.

Antibody testing of serum and CSF samples indicated that

Neospora-specific anti-bodies can react with S neurona

proteins on western blot analysis. The confirmation that

neosporosis in horses can mimic EPM emphasizes the need to

broaden the etiologic definition of EPM beyond infections

exclusively attributable to S neurona.. 0; 0.

303. Massaquoi, S. G.; Slotine, J. J. The intermediate cerebellum may

function as a wave-variable processor. Neurosci-Lett. 1996

Aug 30; 215(1): 60-4; ISSN: 0304-3940.

IRELAND. A newly developed model suggests that the

intermediate cerebellum and spinal cord gray matter may

contribute to movement control by processing control signals

as wave variables. Within specialized communication systems,

wave variables are combinations of forward and return signals

that ensure stable exchange between two sites despite

transmission delays. The composition of signals transmitted

in the ventral spinocerebellar tract appears to be consistent

with that of a wave variable, and computer simulations of the

model yield signals similar to those observed in the monkey

interpositus nucleus. Wave-variable communication may

enable the animal motor system to maintain stable, high-

performance feedback control in the presence of potentially

destabilizing signal transmission delays.

304. Massaquoi, S. G.; Slotine, J. J. The intermediate cerebellum may

function as a wave-variable processor. Neurosci-Lett. 1996

Aug 30; 215(1): 60-4; ISSN: 0304-3940.

IRELAND. A newly developed model suggests that the

intermediate cerebellum and spinal cord gray matter may

contribute to movement control by processing control signals

as wave variables. Within specialized communication systems,

wave variables are combinations of forward and return signals

that ensure stable exchange between two sites despite

transmission delays. The composition of signals transmitted

in the ventral spinocerebellar tract appears to be consistent

with that of a wave variable, and computer simulations of the

model yield signals similar to those observed in the monkey

interpositus nucleus. Wave-variable communication may

enable the animal motor system to maintain stable, high-

performance feedback control in the presence of potentially

destabilizing signal transmission delays.

305. Matesz, C.; Szekely, G. Organization of the ambiguus nucleus in

the frog (Rana esculenta). J-Comp-Neurol. 1996 Jul 22; 371(2):

258-69; ISSN: 0021-9967.

UNITED-STATES. The common root of the glossopharyngeal,

vagal, and accessory nerves and the individual branches of the

vagus complex were labeled with cobalt, and the organization

of the ambiguus nucleus was studied. The cell column labeled

through the common root extended from the upper part of the

medulla to the rostral spinal cord over a distance of about

3,500 microns. The labeling of individual branches revealed

four subdivisions. 1) The pharyngomotor subdivision occupied

the rostral 800 microns of the cell column. It gave origin to

the innervation of the pharyngeal muscles. 2) The visceromotor

subdivision, consisting of small and medium-sized cells

labeled by way of the visceral branches of the vagus, was

found in the rostrocaudal extent of the medulla. 3) the

laryngomotor subdivision extended in the obex region over a

distance of more than 1,000 microns. It supplied the sphincter

muscles of the larynx. The dilator laryngeal muscle was

represented in the rostral part of the visceromotor

subdivision. 4) The accessory nerve subdivision was located in

the lower medulla and the rostral spinal cord. From the

results, the following conclusions are drawn. 1) The basic

organization of the frog ambiguus nucleus is comparable to

that of the rat, differences in nuclear organization reflecting

differences in peripheral structures. 2) The cytoarchitectonic

structure of the four subdivisions innervating different

peripheral targets characteristically differ from each other.

3) On the basis of its characteristic neuronal morphology, the

accessory nerve nucleus is regarded as an independent

structure.

306. Matesz, C.; Szekely, G. Organization of the ambiguus nucleus in

the frog (Rana esculenta). J-Comp-Neurol. 1996 Jul 22; 371(2):

258-69; ISSN: 0021-9967.

UNITED-STATES. The common root of the glossopharyngeal,

vagal, and accessory nerves and the individual branches of the

vagus complex were labeled with cobalt, and the organization

of the ambiguus nucleus was studied. The cell column labeled

through the common root extended from the upper part of the

medulla to the rostral spinal cord over a distance of about

3,500 microns. The labeling of individual branches revealed

four subdivisions. 1) The pharyngomotor subdivision occupied

the rostral 800 microns of the cell column. It gave origin to

the innervation of the pharyngeal muscles. 2) The visceromotor

subdivision, consisting of small and medium-sized cells

labeled by way of the visceral branches of the vagus, was

found in the rostrocaudal extent of the medulla. 3) the

laryngomotor subdivision extended in the obex region over a

distance of more than 1,000 microns. It supplied the sphincter

muscles of the larynx. The dilator laryngeal muscle was

represented in the rostral part of the visceromotor

subdivision. 4) The accessory nerve subdivision was located in

the lower medulla and the rostral spinal cord. From the

results, the following conclusions are drawn. 1) The basic

organization of the frog ambiguus nucleus is comparable to

that of the rat, differences in nuclear organization reflecting

differences in peripheral structures. 2) The cytoarchitectonic

structure of the four subdivisions innervating different

peripheral targets characteristically differ from each other.

3) On the basis of its characteristic neuronal morphology, the

accessory nerve nucleus is regarded as an independent

structure.

307. Matsumoto, A.; Arai, Y.; Prins, G. S. Androgenic regulation of

androgen receptor immunoreactivity in motoneurons of the

spinal nucleus of the bulbocavernosus of male rats. J-

Neuroendocrinol. 1996 Jul; 8(7): 553-9; ISSN: 0953-8194.

ENGLAND. Androgenic regulation of androgen receptor (AR)

immunoreactivity was examined in androgen-sensitive

motoneurons of the spinal nucleus of the bulbocavernosus

(SNB) in adult male rats by immunohistochemistry using the

polyclonal antibody, PG21. In intact controls, intense AR

immunoreactivity was confined to the cell nucleus, but not in

the nucleolus of SNB motoneurons, whereas cytoplasmic AR

immunoreactivity was weak. Androgen withdrawal

significantly reduced both the intensity of AR

immunoreactivity in the nuclei and number of AR

immunoreactive nuclei of the SNB motoneurons within 1 day of

castration. AR immunostaining in the nucleus and cytoplasm

was completely eliminated 5 or 10 days following castration.

These changes were prevented by replacement of testosterone

propionate (TP). The number of AR immunoreactive nuclei

recovered to about half of the control levels within 20 min or

1 hr of TP administration to males 5 days after castration,

although the intensity of AR immunoreactivity was almost the

same as that of males 1 day following castration. Both the

intensity of nuclear and cytoplasmic AR immunoreactivity and

number of AR immunoreactive nuclei recovered to the control

levels 2 or 6 hr after TP injection. These results suggest that

androgen causes a significant up-regulation in AR expression

of SNB motoneurons.. 0; 0; 57-85-2.

308. Matsumoto, A.; Arai, Y.; Prins, G. S. Androgenic regulation of

androgen receptor immunoreactivity in motoneurons of the

spinal nucleus of the bulbocavernosus of male rats. J-

Neuroendocrinol. 1996 Jul; 8(7): 553-9; ISSN: 0953-8194.

ENGLAND. Androgenic regulation of androgen receptor (AR)

immunoreactivity was examined in androgen-sensitive

motoneurons of the spinal nucleus of the bulbocavernosus

(SNB) in adult male rats by immunohistochemistry using the

polyclonal antibody, PG21. In intact controls, intense AR

immunoreactivity was confined to the cell nucleus, but not in

the nucleolus of SNB motoneurons, whereas cytoplasmic AR

immunoreactivity was weak. Androgen withdrawal

significantly reduced both the intensity of AR

immunoreactivity in the nuclei and number of AR

immunoreactive nuclei of the SNB motoneurons within 1 day of

castration. AR immunostaining in the nucleus and cytoplasm

was completely eliminated 5 or 10 days following castration.

These changes were prevented by replacement of testosterone

propionate (TP). The number of AR immunoreactive nuclei

recovered to about half of the control levels within 20 min or

1 hr of TP administration to males 5 days after castration,

although the intensity of AR immunoreactivity was almost the

same as that of males 1 day following castration. Both the

intensity of nuclear and cytoplasmic AR immunoreactivity and

number of AR immunoreactive nuclei recovered to the control

levels 2 or 6 hr after TP injection. These results suggest that

androgen causes a significant up-regulation in AR expression

of SNB motoneurons.. 0; 0; 57-85-2.

309. Matsuzaki, H.; Wakabayashi, K.; Ishihara, K.; Ishikawa, H.;

Kawabata, H.; Onomura, T. The origin and significance of spinal

cord pulsation. Spinal-Cord. 1996 Jul; 34(7): 422-6; ISSN:

1362-4393.

ENGLAND. We studied the origin and mechanism of spinal cord

pulsation in ten dogs in order to elucidate its clinical

significance. Under general anesthesia, a 6 cm length of the

animals' cervical spinal cord was exposed and the

cerebrospinal fluid removed. The amplitude of spinal pulsation

was then measured by means of ultrasonography in Mode M. The

measurements were made after the spinal cord was cut: (1) on

the cranial side; (2) on the cranial as well as caudal side, with

the nerve roots and radicular arteries intact; (3) on both sides

as in (2), which was then supplemented with the severance of

the nerve roots and radicular arteries. It was demonstrated

that, while the pulsation amplitude stood at an average of 88.0

microns before the surgical treatment, it rose to 455.0

microns in (1) and 274.8 microns in (2), but dropped to nearly

zero in (3). The 5.2-fold increase in pulsation following the

cordotomy on the cranial side was attributed to two factors:

(1) the increased spinal mobility due to the cordotomy; (2) the

elevation of blood pressure. The results of the three different

degrees of spinal detachment suggested that spinal pulsation

derived mainly from the radicular arteries and that its

presence indicated low tonicity in the spinal cord and

favorable circulation in the radicular arteries.

310. Matsuzaki, H.; Wakabayashi, K.; Ishihara, K.; Ishikawa, H.;

Kawabata, H.; Onomura, T. The origin and significance of spinal

cord pulsation. Spinal-Cord. 1996 Jul; 34(7): 422-6; ISSN:

1362-4393.

ENGLAND. We studied the origin and mechanism of spinal cord

pulsation in ten dogs in order to elucidate its clinical

significance. Under general anesthesia, a 6 cm length of the

animals' cervical spinal cord was exposed and the

cerebrospinal fluid removed. The amplitude of spinal pulsation

was then measured by means of ultrasonography in Mode M. The

measurements were made after the spinal cord was cut: (1) on

the cranial side; (2) on the cranial as well as caudal side, with

the nerve roots and radicular arteries intact; (3) on both sides

as in (2), which was then supplemented with the severance of

the nerve roots and radicular arteries. It was demonstrated

that, while the pulsation amplitude stood at an average of 88.0

microns before the surgical treatment, it rose to 455.0

microns in (1) and 274.8 microns in (2), but dropped to nearly

zero in (3). The 5.2-fold increase in pulsation following the

cordotomy on the cranial side was attributed to two factors:

(1) the increased spinal mobility due to the cordotomy; (2) the

elevation of blood pressure. The results of the three different

degrees of spinal detachment suggested that spinal pulsation

derived mainly from the radicular arteries and that its

presence indicated low tonicity in the spinal cord and

favorable circulation in the radicular arteries.

311. Mazzone, P.; Pisani, R.; Nobili, F.; Arrigo, A.; Gambaro, M.;

Rodriguez, G. Assessment of regional cerebral blood flow

during spinal cord stimulation in humans. Stereotact-Funct-

Neurosurg. 1995; 64(4): 197-201; ISSN: 1011-6125.

SWITZERLAND. Increased cerebral perfusion has been reported

in both animal models and humans undergoing spinal cord

stimulation (SCS). However, this was an inconsistent finding

and variables able to influence regional cerebral blood flow

(rCBF) following SCS are poorly investigated. We report our

experience on rCBF measurements by the xenon-133 inhalation

technique in 20 patients receiving acute and chronic SCS for

different pathologies in basal conditions. Neither acute nor

chronic SCS induced significant rCBF changes in the group of

patients as a whole. However females, non-atherosclerotic

patients and patients with a cervical SCS lead, showed a trend

(borderline statistical significance) toward a redistribution of

rCBF with increased values in frontoprerolandic and decreased

values in postrolandic regions. Although SCS appears to

influence intracerebral distribution more than absolute

changes in blood flow, the mechanisms underlying such a

phenomenon remain unknown. Functional activation of frontal

lobes by the ascending reticular pathways through the

thalamofrontal projections could be one possible hypothesis

which has to be confirmed by further studies.. 0.

312. Mazzone, P.; Pisani, R.; Nobili, F.; Arrigo, A.; Gambaro, M.;

Rodriguez, G. Assessment of regional cerebral blood flow

during spinal cord stimulation in humans. Stereotact-Funct-

Neurosurg. 1995; 64(4): 197-201; ISSN: 1011-6125.

SWITZERLAND. Increased cerebral perfusion has been reported

in both animal models and humans undergoing spinal cord

stimulation (SCS). However, this was an inconsistent finding

and variables able to influence regional cerebral blood flow

(rCBF) following SCS are poorly investigated. We report our

experience on rCBF measurements by the xenon-133 inhalation

technique in 20 patients receiving acute and chronic SCS for

different pathologies in basal conditions. Neither acute nor

chronic SCS induced significant rCBF changes in the group of

patients as a whole. However females, non-atherosclerotic

patients and patients with a cervical SCS lead, showed a trend

(borderline statistical significance) toward a redistribution of

rCBF with increased values in frontoprerolandic and decreased

values in postrolandic regions. Although SCS appears to

influence intracerebral distribution more than absolute

changes in blood flow, the mechanisms underlying such a

phenomenon remain unknown. Functional activation of frontal

lobes by the ascending reticular pathways through the

thalamofrontal projections could be one possible hypothesis

which has to be confirmed by further studies.. 0.

313. McCarson, K. E.; Krause, J. E. The neurokinin-1 receptor antagonist

LY306,740 blocks nociception-induced increases in dorsal horn

neurokinin-1 receptor gene expression. Mol-Pharmacol. 1996

Nov; 50(5): 1189-99; ISSN: 0026-895X.

UNITED-STATES. Dilute formalin injected into the rat hindpaw

as a nociceptive stimulus increases neurokinin-1 receptor

(NK-1R) mRNA levels in the dorsal horn of the spinal cord.

Increased NK-1R mRNA levels could result from increased

mRNA stability or an increased rate of NK-1R mRNA

transcription. In this study, RNA samples prepared from the

spinal cords of rats receiving an injection of formalin into the

right hindpaw were assayed for NK-1R mRNA with the use of

solution hybridization-nuclease protection assays. The mature

and incompletely spliced NK-1R-encoding RNAs protected by

endogenous rat RNAs were characterized by the use of NK-1R

plasmid constructs containing intron sequences. NK-1R pre-

mRNA species were enriched in the nuclear fractions of spinal

cord samples, and in the steady state, total molar amounts of

NK-1R pre-mRNAs were 2-fold greater than those of mature

NK-1R mRNA. In formalin-treated animals, the temporal

pattern of peak pre-mRNA levels compared with mature mRNA

indicated that chemogenic nociception either activates

transcription of the NK-1R gene or decreases the rate of pre-

mRNA splicing. In the ipsilateral lumbar dorsal hom, NK-1R

mRNA levels were significantly increased at 2 and 6 hr after

formalin injection. Levels of the NK-1R pre-mRNA containing

both introns A and B were significantly increased 1 hr after

formalin treatment, and levels of NK-1R pre-mRNAs containing

intron A were significantly elevated at 2 hr after formalin

treatment. Pretreatment of rats with the selective NK-1R

antagonist LY306,740 was used to determine the role of NK-1R

activation in the regulation of nociception-induced NK-1R

mRNA levels. Rats were pretreated with either LY306,740 or

LY307,679 (an inactive enantiomer) before injection of

formalin into the right hindpaw. Pretreatment with LY306,740

(but not LY307,679) completely blocked the formalin-induced

increase in dorsal horn NK-1R mRNA levels and significantly

reduced formalin-induced behavioral activity. Thus, activation

of the NK-1R during nociception increases dorsal horn NK-1R

mRNA levels through activation of transcriptional or splicing

mechanisms. The stimulation of NK-1R gene expression by

activation of the NK-1R provides a homologous mechanism for

altering the sensitivity of dorsal horn cells to substance P,

potentially via the actions of second messengers, which

presumably results in the maintenance of proper sensory

information processing during long term nociception.. 0; 0; 0;

0; 0; 0; 0; 50-00-0; 63231-63-0.

314. McCarson, K. E.; Krause, J. E. The neurokinin-1 receptor antagonist

LY306,740 blocks nociception-induced increases in dorsal horn

neurokinin-1 receptor gene expression. Mol-Pharmacol. 1996

Nov; 50(5): 1189-99; ISSN: 0026-895X.

UNITED-STATES. Dilute formalin injected into the rat hindpaw

as a nociceptive stimulus increases neurokinin-1 receptor

(NK-1R) mRNA levels in the dorsal horn of the spinal cord.

Increased NK-1R mRNA levels could result from increased

mRNA stability or an increased rate of NK-1R mRNA

transcription. In this study, RNA samples prepared from the

spinal cords of rats receiving an injection of formalin into the

right hindpaw were assayed for NK-1R mRNA with the use of

solution hybridization-nuclease protection assays. The mature

and incompletely spliced NK-1R-encoding RNAs protected by

endogenous rat RNAs were characterized by the use of NK-1R

plasmid constructs containing intron sequences. NK-1R pre-

mRNA species were enriched in the nuclear fractions of spinal

cord samples, and in the steady state, total molar amounts of

NK-1R pre-mRNAs were 2-fold greater than those of mature

NK-1R mRNA. In formalin-treated animals, the temporal

pattern of peak pre-mRNA levels compared with mature mRNA

indicated that chemogenic nociception either activates

transcription of the NK-1R gene or decreases the rate of pre-

mRNA splicing. In the ipsilateral lumbar dorsal hom, NK-1R

mRNA levels were significantly increased at 2 and 6 hr after

formalin injection. Levels of the NK-1R pre-mRNA containing

both introns A and B were significantly increased 1 hr after

formalin treatment, and levels of NK-1R pre-mRNAs containing

intron A were significantly elevated at 2 hr after formalin

treatment. Pretreatment of rats with the selective NK-1R

antagonist LY306,740 was used to determine the role of NK-1R

activation in the regulation of nociception-induced NK-1R

mRNA levels. Rats were pretreated with either LY306,740 or

LY307,679 (an inactive enantiomer) before injection of

formalin into the right hindpaw. Pretreatment with LY306,740

(but not LY307,679) completely blocked the formalin-induced

increase in dorsal horn NK-1R mRNA levels and significantly

reduced formalin-induced behavioral activity. Thus, activation

of the NK-1R during nociception increases dorsal horn NK-1R

mRNA levels through activation of transcriptional or splicing

mechanisms. The stimulation of NK-1R gene expression by

activation of the NK-1R provides a homologous mechanism for

altering the sensitivity of dorsal horn cells to substance P,

potentially via the actions of second messengers, which

presumably results in the maintenance of proper sensory

information processing during long term nociception.. 0; 0; 0;

0; 0; 0; 0; 50-00-0; 63231-63-0.

315. McCrea, D. A. Supraspinal and segmental interactions. Can-J-

Physiol-Pharmacol. 1996 Apr; 74(4): 513-7; ISSN: 0008-4212.

CANADA. For the most part descending systems evoke

movements through spinal interneurons interposed in reflex

pathways. The advantage of this arrangement is that it ensures

an integration of descending commands and proprioceptive and

other exteroceptive feedback during the production of

purposeful movement. It has also become clear that spinal

reflex pathways can be reorganized during movement and that

this could profoundly modify the effects of supraspinal

commands on motor output. Recent experiments illustrate the

existence and regulation of intrinsic motoneuron membrane

currents that can dramatically change how motoneurons

respond to descending commands. To understand how

movements are controlled we must, therefore, understand both

the activity of supraspinal motor systems and the spinal

substrate upon which these commands are exerted.

316. McCrea, D. A. Supraspinal and segmental interactions. Can-J-

Physiol-Pharmacol. 1996 Apr; 74(4): 513-7; ISSN: 0008-4212.

CANADA. For the most part descending systems evoke

movements through spinal interneurons interposed in reflex

pathways. The advantage of this arrangement is that it ensures

an integration of descending commands and proprioceptive and

other exteroceptive feedback during the production of

purposeful movement. It has also become clear that spinal

reflex pathways can be reorganized during movement and that

this could profoundly modify the effects of supraspinal

commands on motor output. Recent experiments illustrate the

existence and regulation of intrinsic motoneuron membrane

currents that can dramatically change how motoneurons

respond to descending commands. To understand how

movements are controlled we must, therefore, understand both

the activity of supraspinal motor systems and the spinal

substrate upon which these commands are exerted.

317. Melsbach, G.; Wohlschlager, A.; Spiess, M.; Gunturkun, O.

Morphological asymmetries of motoneurons innervating upper

extremities: clues to the anatomical foundations of

handedness? Int-J-Neurosci. 1996 Sep; 86(3-4): 217-24; ISSN:

0020-7454.

ENGLAND. Handedness is one of the main issues in laterality

research and is known to be related to a large number of

morphological asymmetries of the central nervous system.

However, the main focus of previous studies were cerebral

structures, which ignored the spinal cord as the most distal

neural entity innervating the muscles of the extremities. We

analyzed morphometrically motoneurons from segments

innervating the arms and hands and compared them with

motoneurons of segments that innervated the upper trunk. We

found an asymmetry with larger motoneuron perikaryas on the

right side of the spinal cord in segments innervating the upper

limbs. To our knowledge this is the first time a morphological

asymmetry on single-cell-level was shown in the spinal cord

of man. The possible relation of this cellular asymmetry to the

origins of handedness is discussed.

318. Melsbach, G.; Wohlschlager, A.; Spiess, M.; Gunturkun, O.

Morphological asymmetries of motoneurons innervating upper

extremities: clues to the anatomical foundations of

handedness? Int-J-Neurosci. 1996 Sep; 86(3-4): 217-24; ISSN:

0020-7454.

ENGLAND. Handedness is one of the main issues in laterality

research and is known to be related to a large number of

morphological asymmetries of the central nervous system.

However, the main focus of previous studies were cerebral

structures, which ignored the spinal cord as the most distal

neural entity innervating the muscles of the extremities. We

analyzed morphometrically motoneurons from segments

innervating the arms and hands and compared them with

motoneurons of segments that innervated the upper trunk. We

found an asymmetry with larger motoneuron perikaryas on the

right side of the spinal cord in segments innervating the upper

limbs. To our knowledge this is the first time a morphological

asymmetry on single-cell-level was shown in the spinal cord

of man. The possible relation of this cellular asymmetry to the

origins of handedness is discussed.

319. Meuli Simmen, C.; Meuli, M.; Hutchins, G. M.; Yingling, C. D.;

Timmel, G. B.; Harrison, M. R.; Adzick, N. S. The fetal spinal cord

does not regenerate after in utero transection in a large

mammalian model. Neurosurgery. 1996 Sep; 39(3): 555-60;

discussion 560-1; ISSN: 0148-396X.

UNITED-STATES. OBJECTIVE: Regeneration and functional

recovery after spinal cord transection do not occur in

mammalian animals and humans postnatally. The goal of this

study was to test whether in utero transection of the fetal

spinal cord is succeeded by anatomic healing and functional

recovery. METHODS: In five sheep fetuses, at 60 days of

gestation and 75 days of gestation (term = 150 d), the spinal

cord was completely transected at T10. The animals were

delivered near term by cesarean section for clinical

evaluation, measurement of cortical somatosensory evoked

potentials, and morphological assessment. RESULTS: The

newborn lambs demonstrated sensory-motor paraplegia, were

incontinent of urine and stool, and exhibited a spinally

generated, ambulatory pattern of the hindlimbs. No cortical

somatosensory evoked potentials could be recorded in response

to posterior tibial nerve stimulation, although potentials from

the ulnar nerve, which enters the cord rostral to the lesion,

were normal in all animals. Histologically, no neuronal

connections across the transection site were identified. The

cord proximal to the lesion was grossly normal, whereas

distal to the transection, it appeared slightly smaller but with

the cytoarchitecture preserved. CONCLUSIONS: Unlike in lower

vertebrate and avian species, the fetal ovine spinal cord has no

detectable spontaneous regenerative capabilities when

transected during midgestation. Gap formation after

transection, secondary posttraumatic cell death, and missing

guiding channels for sprouting axons may be factors involved

in the absence of any regenerative response.

320. Meuli Simmen, C.; Meuli, M.; Hutchins, G. M.; Yingling, C. D.;

Timmel, G. B.; Harrison, M. R.; Adzick, N. S. The fetal spinal cord

does not regenerate after in utero transection in a large

mammalian model. Neurosurgery. 1996 Sep; 39(3): 555-60;

discussion 560-1; ISSN: 0148-396X.

UNITED-STATES. OBJECTIVE: Regeneration and functional

recovery after spinal cord transection do not occur in

mammalian animals and humans postnatally. The goal of this

study was to test whether in utero transection of the fetal

spinal cord is succeeded by anatomic healing and functional

recovery. METHODS: In five sheep fetuses, at 60 days of

gestation and 75 days of gestation (term = 150 d), the spinal

cord was completely transected at T10. The animals were

delivered near term by cesarean section for clinical

evaluation, measurement of cortical somatosensory evoked

potentials, and morphological assessment. RESULTS: The

newborn lambs demonstrated sensory-motor paraplegia, were

incontinent of urine and stool, and exhibited a spinally

generated, ambulatory pattern of the hindlimbs. No cortical

somatosensory evoked potentials could be recorded in response

to posterior tibial nerve stimulation, although potentials from

the ulnar nerve, which enters the cord rostral to the lesion,

were normal in all animals. Histologically, no neuronal

connections across the transection site were identified. The

cord proximal to the lesion was grossly normal, whereas

distal to the transection, it appeared slightly smaller but with

the cytoarchitecture preserved. CONCLUSIONS: Unlike in lower

vertebrate and avian species, the fetal ovine spinal cord has no

detectable spontaneous regenerative capabilities when

transected during midgestation. Gap formation after

transection, secondary posttraumatic cell death, and missing

guiding channels for sprouting axons may be factors involved

in the absence of any regenerative response.

321. Michaloudi, H. C.; Papadopoulos, G. C. Noradrenergic and

dopaminergic systems in the central nervous system of the

hedgehog (Erinaceus europaeus). J-Hirnforsch. 1996; 37(3):

319-50; ISSN: 0021-8359.

GERMANY. The distribution of the noradrenaline (NA)- and

dopamine (DA)-containing neuronal structures in the central

nervous system of the hedgehog (Erinaceus europaeus), a

phylogenetically old mammalian species, was

immunocytochemically studied employing antibodies directed

against the catecholamines (CA) themselves. Groups of DA cell

bodies observed in this study were similar to those present in

other species but the distributional map of the NA-containing

cell bodies exhibited some peculiarities. Prominent among

them were the absence of the A3 group and the paucity of CA

cells in the A2 group. DA neurons in the hypothalamus, apart

from the densely populated paraventricular and arcuate nuclei,

were fewer and less widely distributed than in other species.

In the hedgehog mesencepha- Ion, in contrast to what has been

described in other species, the major DA cell group was

present in the ventral tegmental area. CA immunoreactive

fibers were widely distributed in the CNS of the hedgehog.

However, similarly to what has been observed in other species,

terminal fields of DA neurons were much more restricted when

compared to those of the NA neurons. The neocortical DA

projection system of the hedgehog appeared less developed but

organized similar to that of the rat, and even less developed

than that of the primates. The lack of profound regional and

laminar variations in the density of cortical NA fibers in the

hedgehog enhances the suggestion that the elaboration and

differentiation of the NA cortical system parallels the

phylogenetic development of the cortex. In the brainstem,

interspecies differences in the distribution of the CA fibers

were found to concern primarily some hypothalamic areas

(medial preoptic area, suprachiasmatic nucleus, arcuate

nucleus). Such differences in the thalamus concerned the NA

innervation and they were notably present in the visual

thalamic nuclei (dorsal lateral geniculate nucleus, lateral

posterior thalamic nucleus). In the spinal cord, which was

found to receive fewer CA afferents than those found in other

species, the density of the DA fibers was much lower than that

of the NA axons. In addition to the CNS areas that have been

described in other species to receive catecholaminergic

innervation, the present study showed that both types of

catecholaminergic fibers are distributed in the choroid plexus

and along the ventricular wall of the brain ventricles and the

central canal of the hedgehog.. 51-61-6.

322. Michaloudi, H. C.; Papadopoulos, G. C. Noradrenergic and

dopaminergic systems in the central nervous system of the

hedgehog (Erinaceus europaeus). J-Hirnforsch. 1996; 37(3):

319-50; ISSN: 0021-8359.

GERMANY. The distribution of the noradrenaline (NA)- and

dopamine (DA)-containing neuronal structures in the central

nervous system of the hedgehog (Erinaceus europaeus), a

phylogenetically old mammalian species, was

immunocytochemically studied employing antibodies directed

against the catecholamines (CA) themselves. Groups of DA cell

bodies observed in this study were similar to those present in

other species but the distributional map of the NA-containing

cell bodies exhibited some peculiarities. Prominent among

them were the absence of the A3 group and the paucity of CA

cells in the A2 group. DA neurons in the hypothalamus, apart

from the densely populated paraventricular and arcuate nuclei,

were fewer and less widely distributed than in other species.

In the hedgehog mesencepha- Ion, in contrast to what has been

described in other species, the major DA cell group was

present in the ventral tegmental area. CA immunoreactive

fibers were widely distributed in the CNS of the hedgehog.

However, similarly to what has been observed in other species,

terminal fields of DA neurons were much more restricted when

compared to those of the NA neurons. The neocortical DA

projection system of the hedgehog appeared less developed but

organized similar to that of the rat, and even less developed

than that of the primates. The lack of profound regional and

laminar variations in the density of cortical NA fibers in the

hedgehog enhances the suggestion that the elaboration and

differentiation of the NA cortical system parallels the

phylogenetic development of the cortex. In the brainstem,

interspecies differences in the distribution of the CA fibers

were found to concern primarily some hypothalamic areas

(medial preoptic area, suprachiasmatic nucleus, arcuate

nucleus). Such differences in the thalamus concerned the NA

innervation and they were notably present in the visual

thalamic nuclei (dorsal lateral geniculate nucleus, lateral

posterior thalamic nucleus). In the spinal cord, which was

found to receive fewer CA afferents than those found in other

species, the density of the DA fibers was much lower than that

of the NA axons. In addition to the CNS areas that have been

described in other species to receive catecholaminergic

innervation, the present study showed that both types of

catecholaminergic fibers are distributed in the choroid plexus

and along the ventricular wall of the brain ventricles and the

central canal of the hedgehog.. 51-61-6.

323. Miehe, M.; Leterrier, J. F.; Deloulme, J. C.; Gensburger, C.;

Knoetgen, M. F.; Sensenbrenner, M. Influence of basic fibroblast

growth factor and astroglial cells on the ultrastructure of

developing rat brain neuronal precursors in vitro. Dev-

Neurosci. 1996; 18(3): 210-23; ISSN: 0378-5866.

SWITZERLAND. We have examined the ultrastructural aspect of

neuronal precursors derived from 14-day-old rat embryos

during their development under various culture conditions.

Cells maintained in serum-free medium which have developed

for 1 week in vitro present ultrastructural features of young

neurons. They contain many free ribosomes and microtubules,

but few other organelles and incompletely developed Golgi

apparatus. In the presence of basic fibroblast growth factor

(bFGF), besides cells remaining in aggregates and displaying

morphological features of undifferentiated cells, dispersed

neuroblasts underwent accelerated ultrastructural maturation.

They present well-developed Golgi apparatus, axodendritic

synapses and dense-core vesicles already after 3 days in

culture. By contrast, in the presence of astroglial-conditioned

medium a more homogeneous population developed showing

ultrastructural features of relatively mature neurons.

However, the neuronal precursors acquired the most mature

ultrastructural aspect when they were cocultured with

astroglial cells. The neuronal cell bodies contain highly

developed Golgi complexes, well-differentiated ergastoplasm

and Niss1 body formations, while in the complex neurite

network much more numerous mature synapses with clear and

dense-core vesicles are visible. These observations indicate

that a combination of soluble factors and membrane-bound

factors is essential for extensive ultrastructural development

of neuronal precursors in vitro. Another finding was that in

these cultured neurons neurofilaments (NF) were never seen,

while NF protein subunits were found. These data suggest that

the polymerization of the three NF subunits into intermediate

filaments might need particular cellular factors which

probably do not exist under our in vitro conditions.. 0; 0; 0.

324. Miehe, M.; Leterrier, J. F.; Deloulme, J. C.; Gensburger, C.;

Knoetgen, M. F.; Sensenbrenner, M. Influence of basic fibroblast

growth factor and astroglial cells on the ultrastructure of

developing rat brain neuronal precursors in vitro. Dev-

Neurosci. 1996; 18(3): 210-23; ISSN: 0378-5866.

SWITZERLAND. We have examined the ultrastructural aspect of

neuronal precursors derived from 14-day-old rat embryos

during their development under various culture conditions.

Cells maintained in serum-free medium which have developed

for 1 week in vitro present ultrastructural features of young

neurons. They contain many free ribosomes and microtubules,

but few other organelles and incompletely developed Golgi

apparatus. In the presence of basic fibroblast growth factor

(bFGF), besides cells remaining in aggregates and displaying

morphological features of undifferentiated cells, dispersed

neuroblasts underwent accelerated ultrastructural maturation.

They present well-developed Golgi apparatus, axodendritic

synapses and dense-core vesicles already after 3 days in

culture. By contrast, in the presence of astroglial-conditioned

medium a more homogeneous population developed showing

ultrastructural features of relatively mature neurons.

However, the neuronal precursors acquired the most mature

ultrastructural aspect when they were cocultured with

astroglial cells. The neuronal cell bodies contain highly

developed Golgi complexes, well-differentiated ergastoplasm

and Niss1 body formations, while in the complex neurite

network much more numerous mature synapses with clear and

dense-core vesicles are visible. These observations indicate

that a combination of soluble factors and membrane-bound

factors is essential for extensive ultrastructural development

of neuronal precursors in vitro. Another finding was that in

these cultured neurons neurofilaments (NF) were never seen,

while NF protein subunits were found. These data suggest that

the polymerization of the three NF subunits into intermediate

filaments might need particular cellular factors which

probably do not exist under our in vitro conditions.. 0; 0; 0.

325. Miller, B. A.; Woolf, C. J. Glutamate-mediated slow synaptic

currents in neonatal rat deep dorsal horn neurons in vitro. J-

Neurophysiol. 1996 Sep; 76(3): 1465-76; ISSN: 0022-3077.

UNITED-STATES. 1. The role of glutamate in slow excitatory

synaptic transmission between small-diameter primary

afferents and deep dorsal horn neurons was examined in

neonatal rat spinal cord in vitro with the use of the whole cell

voltage-clamp technique. 2. Single-shock electrical

stimulation of large-diameter A beta-fibers evoked a short-

latency (< 10 ms) fast (< 500 ms) excitatory postsynaptic

current (EPSC). Stimulation of small-diameter A delta- and C

fibers resulted, in addition, in a slowly rising and decaying

EPSC (lasting up to 14 s) following the fast EPSC. The slow

EPSC was never observed with stimulation of A beta-fibers. 3.

Two patterns of EPSCs were observed, "type 1" and "type 2,"

which differed in their time course (lasting up to 1 and 14 s,

respectively). The type 1 response was biphasic, with a fast

monosynaptic component followed by an invariant, presumably

monosynaptic, late slow component. The type 2 response was

multiphasic, with a fast monosynaptic component followed by

a slow component composed of fast polysynaptic currents

superimposed on a slow current. 4. The fast monosynaptic

component had a linear conductance, whereas the late slower

component of the A beta-fiber-evoked response had a negative

slope conductance at holding potentials more negative than -

23 mV. Both currents reversed at a membrane potential of -1.2

+/- 2.8 (SE) mV. 5. With the use of selective non-N-methyl-D-

aspartate (non-NMDA) and NMDA receptor antagonists [6-

cyano-7-nitroquinox-aline-2,3-dione (CNQX) or 2,3-dihydroxy-

6-nitro-7-sulphamoyl-benzo (F) quinoxaline and D(-)-2-

amino-5-phosphonopentanoic acid (D-AP5), respectively] we

showed that both the early fast (A beta-fiber evoked) and the

late slow (A delta- and C fiber evoked) components were

mediated by non-NMDA and NMDA receptors. CNQX suppressed

both the early fast and late slow components of the compound

EPSC, whereas D-AP5 suppressed the polysynaptic currents of

the early fast component and the late slow component without

significantly affecting the early fast monosynaptic component.

6. Slow EPSCs summated on low-frequency (1 or 10 Hz),

repetitive stimulation and produced long-duration "tail"

currents on cessation of the stimulus. The amount of temporal

summation was proportional to the duration of the slow EPSC

and the frequency of stimulation. 7. Our results suggest that

slow ionotropic-glutamate-receptor-mediated EPSCs produced

by the stimulation of small-diameter primary afferents play

an important role in activity-dependent synaptic plasticity in

the dorsal horn.. 0; 0; 0; 0; 56-86-0; 7440-46-2.

326. Miller, B. A.; Woolf, C. J. Glutamate-mediated slow synaptic

currents in neonatal rat deep dorsal horn neurons in vitro. J-

Neurophysiol. 1996 Sep; 76(3): 1465-76; ISSN: 0022-3077.

UNITED-STATES. 1. The role of glutamate in slow excitatory

synaptic transmission between small-diameter primary

afferents and deep dorsal horn neurons was examined in

neonatal rat spinal cord in vitro with the use of the whole cell

voltage-clamp technique. 2. Single-shock electrical

stimulation of large-diameter A beta-fibers evoked a short-

latency (< 10 ms) fast (< 500 ms) excitatory postsynaptic

current (EPSC). Stimulation of small-diameter A delta- and C

fibers resulted, in addition, in a slowly rising and decaying

EPSC (lasting up to 14 s) following the fast EPSC. The slow

EPSC was never observed with stimulation of A beta-fibers. 3.

Two patterns of EPSCs were observed, "type 1" and "type 2,"

which differed in their time course (lasting up to 1 and 14 s,

respectively). The type 1 response was biphasic, with a fast

monosynaptic component followed by an invariant, presumably

monosynaptic, late slow component. The type 2 response was

multiphasic, with a fast monosynaptic component followed by

a slow component composed of fast polysynaptic currents

superimposed on a slow current. 4. The fast monosynaptic

component had a linear conductance, whereas the late slower

component of the A beta-fiber-evoked response had a negative

slope conductance at holding potentials more negative than -

23 mV. Both currents reversed at a membrane potential of -1.2

+/- 2.8 (SE) mV. 5. With the use of selective non-N-methyl-D-

aspartate (non-NMDA) and NMDA receptor antagonists [6-

cyano-7-nitroquinox-aline-2,3-dione (CNQX) or 2,3-dihydroxy-

6-nitro-7-sulphamoyl-benzo (F) quinoxaline and D(-)-2-

amino-5-phosphonopentanoic acid (D-AP5), respectively] we

showed that both the early fast (A beta-fiber evoked) and the

late slow (A delta- and C fiber evoked) components were

mediated by non-NMDA and NMDA receptors. CNQX suppressed

both the early fast and late slow components of the compound

EPSC, whereas D-AP5 suppressed the polysynaptic currents of

the early fast component and the late slow component without

significantly affecting the early fast monosynaptic component.

6. Slow EPSCs summated on low-frequency (1 or 10 Hz),

repetitive stimulation and produced long-duration "tail"

currents on cessation of the stimulus. The amount of temporal

summation was proportional to the duration of the slow EPSC

and the frequency of stimulation. 7. Our results suggest that

slow ionotropic-glutamate-receptor-mediated EPSCs produced

by the stimulation of small-diameter primary afferents play

an important role in activity-dependent synaptic plasticity in

the dorsal horn.. 0; 0; 0; 0; 56-86-0; 7440-46-2.

327. Momiyama, A.; Feldmeyer, D.; Cull Candy, S. G. Identification of a

native low-conductance NMDA channel with reduced

sensitivity to Mg2+ in rat central neurones. J-Physiol-Lond.

1996 Jul 15; 494( Pt 2): 479-92; ISSN: 0022-3751.

ENGLAND. 1. We have identified a new type of NMDA channel in

rat central neurones that express mRNA for the NR2D subunit.

We have examined single NMDA channels in cerebellar Purkinje

cells (which possess NR1 and 2D), deep cerebellar nuclei (NR1,

2A, 2B and 2D) and spinal cord dorsal horn neurones (NR1, 2B

and 2D). 2. In Purkinje cells, NMDA opened channels with a

main conductance of 37.9 +/- 1.1 pS and a subconductance of

17.8 +/- 0.7 pS, with frequent transitions between the two

levels. 3. NMDA activated low-conductance ('38/18 pS') events

(along with high-conductance--'50/40 pS'--openings) in some

patches from deep cerebellar nuclei and dorsal horn neurones.

Our evidence suggests that 38/18 pS and 50/40 pS events

arose from distinct types of NMDA receptors. 4. The

transitions for 38/18 pS events were asymmetrical: steps

from 38 to 18 pS were more frequent (72.2%) than steps from

18 to 38 pS. This feature appeared common to the 38/18 pS

events in all three cell types, suggesting similarity in the

low-conductance channels. 5. The 38/18 pS channels in

Purkinje cells exhibited characteristic NMDA receptor

properties, including requirement for glycine, antagonism by

D-2-amino-5-phosphonopentanoic acid (D-AP5) and 7-

chlorokynurenic acid, and voltage-dependent block by

extracellular Mg2+. 6. The mean open time for the 38 pS state

(0.74 +/- 0.07 ms) was significantly briefer than that for the

18 pS state (1.27 +/- 0.18 ms). 7. Mg2+ block of low-

conductance NMDA channels in Purkinje cells was less marked

than block of 50/40 pS channels in cerebellar granule cells. 8.

The time course of appearance of 38/18 pS NMDA channels

matched the expression of mRNA for the NR2D subunit. Thus

38/18 pS events were present in > 70% of Purkinje cell

patches in 0- to 8-day-old animals, and absent by postnatal

day 12. 9. We propose that the 38/18 pS NMDA channels

identified here (associated with the NR2D subunit), and the

other low-conductance NMDA channel associated with the

NR2C subunit, may together constitute a functionally distinct

subclass of native NMDA receptors.. 0; 0; 0; 18000-24-3; 492-

27-3; 7439-95-4; 76726-92-6.

328. Momiyama, A.; Feldmeyer, D.; Cull Candy, S. G. Identification of a

native low-conductance NMDA channel with reduced

sensitivity to Mg2+ in rat central neurones. J-Physiol-Lond.

1996 Jul 15; 494( Pt 2): 479-92; ISSN: 0022-3751.

ENGLAND. 1. We have identified a new type of NMDA channel in

rat central neurones that express mRNA for the NR2D subunit.

We have examined single NMDA channels in cerebellar Purkinje

cells (which possess NR1 and 2D), deep cerebellar nuclei (NR1,

2A, 2B and 2D) and spinal cord dorsal horn neurones (NR1, 2B

and 2D). 2. In Purkinje cells, NMDA opened channels with a

main conductance of 37.9 +/- 1.1 pS and a subconductance of

17.8 +/- 0.7 pS, with frequent transitions between the two

levels. 3. NMDA activated low-conductance ('38/18 pS') events

(along with high-conductance--'50/40 pS'--openings) in some

patches from deep cerebellar nuclei and dorsal horn neurones.

Our evidence suggests that 38/18 pS and 50/40 pS events

arose from distinct types of NMDA receptors. 4. The

transitions for 38/18 pS events were asymmetrical: steps

from 38 to 18 pS were more frequent (72.2%) than steps from

18 to 38 pS. This feature appeared common to the 38/18 pS

events in all three cell types, suggesting similarity in the

low-conductance channels. 5. The 38/18 pS channels in

Purkinje cells exhibited characteristic NMDA receptor

properties, including requirement for glycine, antagonism by

D-2-amino-5-phosphonopentanoic acid (D-AP5) and 7-

chlorokynurenic acid, and voltage-dependent block by

extracellular Mg2+. 6. The mean open time for the 38 pS state

(0.74 +/- 0.07 ms) was significantly briefer than that for the

18 pS state (1.27 +/- 0.18 ms). 7. Mg2+ block of low-

conductance NMDA channels in Purkinje cells was less marked

than block of 50/40 pS channels in cerebellar granule cells. 8.

The time course of appearance of 38/18 pS NMDA channels

matched the expression of mRNA for the NR2D subunit. Thus

38/18 pS events were present in > 70% of Purkinje cell

patches in 0- to 8-day-old animals, and absent by postnatal

day 12. 9. We propose that the 38/18 pS NMDA channels

identified here (associated with the NR2D subunit), and the

other low-conductance NMDA channel associated with the

NR2C subunit, may together constitute a functionally distinct

subclass of native NMDA receptors.. 0; 0; 0; 18000-24-3; 492-

27-3; 7439-95-4; 76726-92-6.

329. Motorina, M. V. [The ultrastructural characteristics of the

sensorimotor synapses in the amphibian spinal cord].

Ul'trastrukturnye osobennosti sensomotornykh sinapsov v

spinnom mozge amfibii. Morfologiia. 1996; 110(4): 48-55;

ISSN: 0004-1947.

RUSSIA. The present electron microscopic study aims to

analyse sensomotor synapses ultrastructural peculiarities in

part deafferentation and neuroplasmic transport to horse-

radish peroxidase through the sectioned dorsal radix. Three

zones of primary afferent fibres endings, including motor

nuclear zone were found in the amphibian spinal cord. The data

obtained demonstrated the probability of both chemical and

combined (electrochemical, mostly of axodendritic type) origin

of synapses, formed by primary afferent fibres on motor

neurons somato-dendritic membrane. Complex synapses are

likely to acquire peculiar importance in deafferentation. These

data correlate with microphysiological research on amphibians

sensomotor synaptic contacts.. EC 1.11.1.-.

330. Motorina, M. V. [The ultrastructural characteristics of the

sensorimotor synapses in the amphibian spinal cord].

Ul'trastrukturnye osobennosti sensomotornykh sinapsov v

spinnom mozge amfibii. Morfologiia. 1996; 110(4): 48-55;

ISSN: 0004-1947.

RUSSIA. The present electron microscopic study aims to

analyse sensomotor synapses ultrastructural peculiarities in

part deafferentation and neuroplasmic transport to horse-

radish peroxidase through the sectioned dorsal radix. Three

zones of primary afferent fibres endings, including motor

nuclear zone were found in the amphibian spinal cord. The data

obtained demonstrated the probability of both chemical and

combined (electrochemical, mostly of axodendritic type) origin

of synapses, formed by primary afferent fibres on motor

neurons somato-dendritic membrane. Complex synapses are

likely to acquire peculiar importance in deafferentation. These

data correlate with microphysiological research on amphibians

sensomotor synaptic contacts.. EC 1.11.1.-.

331. Myers, M. R. A numerical investigation into factors affecting

anesthetic distribution during spinal anesthesia. J-Biomech.

1996 Feb; 29(2): 139-49; ISSN: 0021-9290.

UNITED-STATES. The factors affecting distribution of

anesthetic within the spinal column are of current interest

due to recent reports of neurological injury occurring during

spinal anesthesia. This paper describes a numerical model for

simulating anesthetic dispersion, and applies the model to the

evaluation of spinal-column size, anesthetic injection rate,

and catheter orientation as factors influencing the anesthetic

distribution. The model is based upon the finite-element

method and incorporates a three-dimensional geometry derived

from images of human spinal columns. Simulation results show

that the ratio of the cross-sectional dimension of the

subarachnoid space within the spinal column to the diameter

of the catheter is a critical parameter, with low values of this

ratio producing the most uniform anesthetic distributions.

Increasing injection rate is found to produce a less uniform

distribution in a global sense (higher total volume of

anesthetic in the 'sacral' half) but a more uniform distribution

in a localized sense (lower concentrations at critical points).

Finally, the anesthetic distribution is demonstrated to be

highly sensitive to orientation angle at high injection rates..

0.

332. Myers, M. R. A numerical investigation into factors affecting

anesthetic distribution during spinal anesthesia. J-Biomech.

1996 Feb; 29(2): 139-49; ISSN: 0021-9290.

UNITED-STATES. The factors affecting distribution of

anesthetic within the spinal column are of current interest

due to recent reports of neurological injury occurring during

spinal anesthesia. This paper describes a numerical model for

simulating anesthetic dispersion, and applies the model to the

evaluation of spinal-column size, anesthetic injection rate,

and catheter orientation as factors influencing the anesthetic

distribution. The model is based upon the finite-element

method and incorporates a three-dimensional geometry derived

from images of human spinal columns. Simulation results show

that the ratio of the cross-sectional dimension of the

subarachnoid space within the spinal column to the diameter

of the catheter is a critical parameter, with low values of this

ratio producing the most uniform anesthetic distributions.

Increasing injection rate is found to produce a less uniform

distribution in a global sense (higher total volume of

anesthetic in the 'sacral' half) but a more uniform distribution

in a localized sense (lower concentrations at critical points).

Finally, the anesthetic distribution is demonstrated to be

highly sensitive to orientation angle at high injection rates..

0.

333. Nadon, N. L.; Duncan, I. D. Molecular analysis of glial cell

development in the canine 'shaking pup' mutant. Dev-Neurosci.

1996; 18(3): 174-84; ISSN: 0378-5866.

SWITZERLAND. The shaking pup, a canine mutant, carries a

point mutation in the myelin proteolipid protein (PLP) gene

that causes dysmyelination of the central nervous system

(CNS) with resultant tremor, seizures, and other persistent

neurological deficits. The developmental potential of glial

cells in the shaking pup CNS and peripheral nervous system

(PNS) was evaluated by quantitative analysis of the expression

of several glial-specific genes. All of the myelin-associated

genes demonstrated developmental patterns of expression

similar to those observed in the controls, but at significantly

reduced levels. Expression of the genes for the major CNS

myelin proteins, PLP and the myelin basic protein, are most

dramatically affected in the shaking pup, although reduced

expression levels are observed for other oligodendrocyte-

specific genes such as 2',3'-cyclic nucleotide

3'phosphodiesterase and glucose phosphate dehydrogenase. The

pattern of gene expression in the shaking pup indicates that

the oligodendrocytes experience an inhibition in development

after the myelination program has begun. There appears to be

little evidence for an astrocytic response to the

dysmyelinating condition at the RNA level, but we present

evidence for ectopic expression of P0 mRNA in the CNS.

Expression of the P0 and PLP genes in the sciatic nerve

appears to be normal, reinforcing previous reports that PNS

myelination is unaffected by the mutation in the PLP gene.. 0;

0; 0; 0.

334. Nadon, N. L.; Duncan, I. D. Molecular analysis of glial cell

development in the canine 'shaking pup' mutant. Dev-Neurosci.

1996; 18(3): 174-84; ISSN: 0378-5866.

SWITZERLAND. The shaking pup, a canine mutant, carries a

point mutation in the myelin proteolipid protein (PLP) gene

that causes dysmyelination of the central nervous system

(CNS) with resultant tremor, seizures, and other persistent

neurological deficits. The developmental potential of glial

cells in the shaking pup CNS and peripheral nervous system

(PNS) was evaluated by quantitative analysis of the expression

of several glial-specific genes. All of the myelin-associated

genes demonstrated developmental patterns of expression

similar to those observed in the controls, but at significantly

reduced levels. Expression of the genes for the major CNS

myelin proteins, PLP and the myelin basic protein, are most

dramatically affected in the shaking pup, although reduced

expression levels are observed for other oligodendrocyte-

specific genes such as 2',3'-cyclic nucleotide

3'phosphodiesterase and glucose phosphate dehydrogenase. The

pattern of gene expression in the shaking pup indicates that

the oligodendrocytes experience an inhibition in development

after the myelination program has begun. There appears to be

little evidence for an astrocytic response to the

dysmyelinating condition at the RNA level, but we present

evidence for ectopic expression of P0 mRNA in the CNS.

Expression of the P0 and PLP genes in the sciatic nerve

appears to be normal, reinforcing previous reports that PNS

myelination is unaffected by the mutation in the PLP gene.. 0;

0; 0; 0.

335. Nagy, I.; Woolf, C. J. Lignocaine selectively reduces C fibre-

evoked neuronal activity in rat spinal cord in vitro by

decreasing N-methyl-D-aspartate and neurokinin receptor-

mediated post-synaptic depolarizations; implications for the

development of novel centrally acting analgesics. Pain. 1996

Jan; 64(1): 59-70; ISSN: 0304-3959.

NETHERLANDS. The action of lignocaine on nociceptive

transmission in the spinal cord has been studied in vitro using

ventral root potential (VRP) recordings from 10-12-day-old

rat hemisected spinal cord preparations. Single-shock

stimulation of a dorsal root at intensities sufficient to

activate high-threshold C-primary afferent fibres elicited

VRPs lasting for 15-20 sec in the corresponding ventral root.

The VRP consisted of 3 distinct parts: the early, slow and

prolonged components, as previously described (Thompson et

al. 1992), where the early represents A beta fibre-evoked

mono- and polysynaptic responses lasting for tens of

milliseconds, the slow is a largely N-methyl-D-aspartic acid

(NMDA) receptor-mediated small-calibre afferent-generated

component, lasting for about 1.5 sec, and the prolonged is a

neurokinin receptor-mediated long-lasting component

generated by high-threshold fibres. Lignocaine superfusion

(40-60 microM) significantly and reversibly reduced the slow

and prolonged components of the C fibre-evoked VRP in a dose-

dependent manner without any effect on the early or A beta

fibre-mediated component of the VRP. The amplitude of the

cumulative VRP generated by repetitive inputs (1 and 10 Hz)

was also significantly reduced as was the depolarization

produced by bath application of NMDA (100 microM) or

substance P (SP, 1 microM) in the presence or absenc