Biomedical subjects

J M Billard

Publications and source records attributed to J M Billard.

At least 37 records · Page 2Linked to original sources

PubMed1993

Pre- and postsynaptic GABAB receptors of rat neocortical neurons differ in their pharmacological properties.

GABA (gamma-amino butyric acid)B receptors have been proposed to play a dual role in synaptic transmission in the mammalian central nervous system (CNS): they participate in a late inhibitory postsynaptic potential (1-IPSP) and reduce the release of GABA by a presynaptic action. To further characterize these mechanisms, two established GABAB receptor antagonists were applied to intracellularly recorded rat neocortical neurons in vitro. The depression of the 1-IPSP by the GABAB receptor antagonists phaclofen and 2-OH-saclofen averaged 30% and 50%, respectively. Phaclofen had no effect on direct excitability or excitatory synaptic transmission. The depression of a second IPSP evoked by paired-pulse stimulation was used as an index for presynaptic GABAB receptor activation. Neither antagonist exerted significant effects on this transient depression of GABAergic inhibition. The present results suggest that the pre- and postsynaptic GABAB receptors involved in GABAergic transmission of neocortical neurons differ in their pharmacological properties.

Animals↗

PubMed1993

GABA, THIP and baclofen inhibition of Purkinje cells and cerebellar nuclei neurons.

The sensitivity of Purkinje cells (PCs) and neurons of the cerebellar nuclei (NCNs) to iontophoretic application of gamma-aminobutyric acid (GABA), 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) and baclofen, i.e., GABAA and GABAB agonists respectively, have been studied in anesthetized rats. All the agonists produced dose-dependent firing rate depression of the PCs but with different potencies. The inhibitory actions of both GABA and THIP were specifically antagonized by bicuculline (Bic) and the baclofen-induced responses by 2-hydroxysaclofen. GABA and THIP also depressed the spontaneous activity of NCNs while baclofen was ineffective. The present results therefore suggest that GABAA receptors are involved in the GABA-induced inhibition in the cerebellar cortex and in the cerebellar nuclei and GABAB receptors are involved only in the cerebellar cortex.

Animals↗

PubMed1993

Reduction of GABA inhibition in Purkinje and cerebellar nuclei neurons in climbing fibre deafferented cerebella of rat.

GABA agonists were iontophoretically applied to Purkinje cells (PCs) of the cerebellar cortex and to neurons of the cerebellar nuclei (NCNs) in normal and in climbing fibre (CF) deafferented cerebella of rat. The experiments were performed one and three months after CF deafferentation obtained by total inferior olive destruction with 3-acetylpyridine. All control PCs were dose-dependently inhibited by GABA and muscimol and nearly all by baclofen. After CF deafferentation, the number of PCs sensitive to muscimol remained the same but the number sensitive to baclofen was greatly reduced one month later and almost absent after three months. The number of NCNs inhibited by GABA was slightly reduced one month after deafferentation compared to controls, but reduced to less than half three months after. Thus CF deafferentation of the PC leads to changes in postsynaptic sensitivity to GABA, the presumed inhibitory neurotransmitter, affecting GABAA receptors of the NCNs and GABAB receptors of the PCs.

Animals↗

PubMed1991

Sensitivity of rubrospinal neurons to excitatory amino acids in the rat red nucleus in vivo.

Responses of rubrospinal neurons (RSNs) to iontophoretic applications of L-glutamate (L-Glu), L-aspartate (L-Asp), quisqualate (Quis) and N-methyl-D-aspartate (NMDA) have been studied in the rat red nucleus (RN) in vivo. All agonists produced a dose-dependent increase of the firing rate and Quis was found to be the most efficient. The responses to NMDA and to a lesser extent to L-Asp were abolished by steady application of 2-amino-5-phosphonovalerate (2APV) whereas responses to Quis were unaffected and those to L-Glu poorly antagonized. On the other hand, NMDA-mediated excitations were insensitive to steady application of 6,7-dinitroquinoxaline-2,3-dione (DNQX) which abolished responses to Quis and to a lesser extent to L-Glu while those to L-Asp were less affected. These results show the presence of both NMDA and non-NMDA receptors on RSNs in the rat. A specific localization of the NMDA receptors on distal dendrites of these neurons is suggested.

2-Amino-5-phosphonovalerate↗

PubMed1991

Tetrodotoxin induced calcium spikes: in vitro and in vivo studies of normal and deafferented Purkinje cells.

Tetrodotoxin (TTX) is widely used to block the sodium dependent action potential in excitable cells to study their other ionic properties. TTX applied outside, selectively blocks voltage dependent sodium channels and is thought to have no other effects. We report here that TTX, applied to slices of rat cerebellum, suppressed sodium spikes of the Purkinje cells and induced firing in bursts of slower spikes. This activity was blocked by cobalt (2 mM) or cadmium (0.2 mM) in the medium as well as by hyperpolarizing currents showing that the slow spikes were due to voltage dependent calcium channels. The membrane potential was not significantly changed by TTX and the spikes during the bursts had the same threshold potentials and peak spike amplitudes as the voltage and Ca2+ dependent dendritic spikes evoked by injected current before adding TTX. This indicated that no marked changes in the membrane conductances were produced by the TTX. Unlike the burst firing induced by removing extracellular sodium, the TTX induced bursts were not followed by a large hyperpolarization. The same kind of results were obtained with extracellular recording in the in-vivo preparation with TTX applied topically or by pressure near the recording sites. TTX induced burst firing was not due to blocking afferent inhibitory input to the PC, since bicuculline (10(-6) M) applied without TTX, produced only increased firing of fast action potentials and no bursts. The bursts could be arrested within 1 to 2 min by intravenously administering 2 mg/kg sodium pentobarbital, the blockage lasted from 5 to 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1991

Decreased sensitivity of cerebellar nuclei neurons to GABA and taurine: effects of long-term inferior olive destruction in the rat.

The effects of iontophoretically applying the presumed Purkinje cell inhibitory neurotransmitters, GABA and taurine, were tested on neurons of the cerebellar nuclei in normal and in climbing-fiber-deafferented cerebella. Rats treated with 3-acetylpyridine to totally destroy the inferior olive were used for acute experiments 105-185 days after treatment. In controls, nearly all neuronal firing was dose-dependently depressed by both inhibitory amino acids. The depression in firing for both were antagonized by bicuculline and picrotoxin but not by strychnine while TAG specifically antagonized only responses to taurine. At sufficient doses, bicuculline and TAG induced disinhibitory responses (significant release of neuron discharge) in the absence of applied antagonist. In deafferented animals, the inhibitory efficacy of GABA and taurine were drastically reduced; most of the neurons failed to respond to these amino acids at the same iontophoretic parameters as for the control rats. Moreover, high doses of bicuculline and TAG did not induce any disinhibitory response (no significant increase in discharge rate) in most of the neurons tested. These results clearly demonstrate that climbing fiber deafferentation reduces postsynaptic sensitivity of the cerebellar nuclei neurons for the presumed Purkinje cell inhibitory neurotransmitters.

Action Potentials↗

PubMed1990

Taurine in deep cerebellar nuclei of the rat. In vivo comparison to GABA inhibitory effect.

The sensitivity of neurons of the deep cerebellar nuclei to iontophoretic application of taurine (TAU) and gamma-aminobutyric acid (GABA) has been studied in vivo in rats. Both TAU and GABA produced a dose-dependent depression of the firing rate. Both the inhibitory actions of TAU and GABA were antagonized by bicuculline (BIC) and picrotoxin (PIC) but not by strychnine (STRY) meaning that TAU had a 'GABA-like' effect in the deep cerebellar nuclei. Simultaneous application of TAU and GABA induced not an additive but a synergistic inhibitory effect on the discharge of the neurons of the interposed and dentate nuclei. These results indicate the involvement of TAU in the inhibitory processes acting on neurons of the deep cerebellar nuclei.

Action Potentials↗

PubMed1989

Loss of N-methyl-D-aspartate sensitivity of cerebellar Purkinje cells after climbing fiber deafferentation. An in vivo study in the rat.

The sensitivity of cerebellar Purkinje cells to brief iontophoretic applications of excitatory amino acids has been studied in vivo in rats treated from 15 days to 4 months beforehand with 3-acetylpyridine in order to destroy the inferior olive. Responses of Purkinje cells (PCs) chronically deprived of climbing fibers were thus investigated using extracellular microelectrodes and compared to those of a group of control rats. No changes in the relative efficiencies of L-glutamate, L-aspartate, quisqualate and kainate have been observed. In contrast, the excitations induced by N-methyl-D-aspartate (NMDA) on most PCs in control animals, were no longer present after climbing fiber deprivation. These results show that both NMDA and non-NMDA receptors are present on PCs of adult rodents and that the NMDA responses are strongly depressed when PCs are deafferented of the climbing fibers.

Amino Acids↗

PubMed1988

Persistent reduction of Purkinje cell inhibition on neurones of the cerebellar nuclei after climbing fibre deafferentation.

The long lasting effects of inferior olive (IO) destruction were studied in rats treated with 3-acetylpyridine two years before. The activities of the Purkinje cells (PCs) and of their target neurones in the cerebellar nuclei (ECNs), were investigated and compared to those of a group of non-treated rats. Our results show that long-term deafferented PCs recovered a mean firing frequency similar to that of the controls while the ECNs discharge is enhanced. Furthermore, the cryodestruction of the cerebellar cortex produces a significant release of the ECNs firing in the control rats but not in the poisoned animals. Thus, it appears that IO destruction induces a permanent impairment of the inhibitory control exerted by the PCs on the activity of their target neurones.

Afferent Pathways↗

PubMed1987

The interposito-rubrospinal system. Anatomical tracing of a motor control pathway in the rat.

The cerebello-rubromotor pathway, impinging on both spinal and facial motor nuclei, has been traced in the rat, using the bidirectional transport of horseradish peroxidase-wheat germ agglutinin conjugate. After injection of the tracer in the red nucleus (NR), retrograde labelling shows a topical arrangement of the cerebellorubral connection. The nucleus lateralis projects to the parvocellular NR (NRp) and the nucleus interpositus to the magnocellular NR (NRm). The nucleus interpositus anterior (NIA) reaches the entire NRm and this projection is topographically arranged: the medial NIA sends fibres ventrally, the lateral NIA dorsally. The medial two-thirds of the nucleus interpositus posterior (NIP) project only to the medial aspect of the NRm, with no apparent organization. No connection has been found between the lateral third of NIP and the NRm. After injection of the tracer in the spinal cord or the nucleus of the facial nerve, retrograde labelling is observed almost throughout the entire caudorostral extent of the NR, although labelling is more scant in NRp than in NRm. Rubrospinal and rubrofacial projections are somatotopically arranged in the dorsoventral direction: ventrolateral regions of NR reach the lumbar cord, medioventral regions the lower cervical levels, intermediary regions the upper cervical levels and finally the dorsalmost part of the NR projects to the nucleus of the facial nerve. After injection of the tracer in the cerebellar nuclei, anterograde labelling in the NR shows that interpositorubral connections determine two subregions in the NR: a lateral one under the exclusive control of the NIA, and a medial one under the control of both NIA-NIP afferents. It confirms in addition the topography of the NIA-NRm projection and shows the preponderant participation of the NIA afferents to the interpositorubral connection. Thus, it appears from our results that the cerebellorubral arrangement matches, to a great extent, the "rubromotor" efferent organization.

Animals↗

PubMed1986

The cerebellorubral projection in the rat: retrograde anatomical study.

The cerebellorubral projections have been studied in the rat using the retrograde transport of horseradish peroxidase-wheat germ agglutinin conjugate. The lateral cerebellar nucleus projects to the parvocellular red nucleus (RN), the anterior (NIA) and posterior (NIP) interposed nuclei project to the magnocellular RN. Whereas the projections from the NIP are limited to the medial aspect of the RN, those from the NIA extend throughout the magnocellular RN. NIA-RN projections are topographically arranged: the medial NIA projects ventrally, the lateral NIA projects dorsally. Functionally, this differential distribution seems to fit the hindlimb-forelimb areas of origin of the rubrospinal tract.

Animals↗

PubMed1986

Long term modification of rubral activity after inferior olive destruction.

The long term effects of the inferior olive degeneration on red nucleus activity were studied in the rat. The animals were injected with 3-acetylpyridine to produce a pharmacological destruction of the inferior olive and were then used for acute experiments at 1-2, 5-7, 14-18, 29-37, 81-110 and 236-255 days later. After degeneration of the inferior olive, there was an 'initial period' lasting for a few days, characterized by a low discharge frequency of the red nucleus neurones. A 'period of adaptation' followed during the first month, characterized by a slow recovery towards the control firing rates of the rubral units. Nevertheless, the temporal distribution of the discharges was not recovered since the firing became organized in a bursting activity. From 1 up to 8 months, the normal unit activity was not restored. The hypothesis is advanced that the suppression of the inferior olive which increases the cerebellar inhibition, produces a consequent disfacilitation of red nucleus activity which persists for a few days. Then at increasing survival times, a progressive compensation takes place without a real restoration of the initial rubral activity.

Action Potentials↗

PubMed1985

Inferior olive destruction induces dysfacilitation of the red nucleus activity.

The spontaneous discharge frequency of the red nucleus neurones was evaluated in rat before and after total destruction of the inferior olive with the 3-acetylpyridine. It was found that the sustained firing recorded in the control animals (33.7 +/- 23.7/s) drastically decreased to a low rate (4.6 +/- 7.1/s) after the intoxication. This effect took place between 2 h 15 min and 2 h 45 min after the injection. which is the critical period corresponding to the inferior olive degeneration and the consequent climbing fiber deafferentation. It lasted at least as long as the acute experiment. The conclusions are reached that the inferior olive destruction leading to an enhanced cerebellar inhibition, produces a dysfacilitatory effect on the red nucleus neurones.

Animals↗

PubMed1985

Long term modification of cerebellar inhibition after inferior olive degeneration.

The long term effects of inferior olive destruction on the activities of the Purkinje cells and their target neurones in the cerebellar nuclei were studied in the rat. Careful observations were also made of motor behaviour throughout the study. Albino rats were injected with 3-acetylpyridine to produce a neurotoxic destruction of the inferior olive and then were used for acute recording experiments at 1-2 days, 5-7 days, 12-18 days, 35-38 days, 75-97 days and 230-252 days. After degeneration of the inferior olive, there was an initial period lasting for a few days, characterized by a high firing frequency of Purkinje cells associated with a very low level of activity of the neurones in the cerebellar nuclei. During this period, there was a deep depression of motor activity. A period of adaptation follows during the first month, characterized by a slow recovery of the initial firing frequency of the cerebellar units and a gradual recovery of spontaneous locomotion; nevertheless the firing pattern and motor behaviour remain abnormal. From one month on the unit activities disturbances and the motor deficiencies stabilize. The hypothesis is advanced that Purkinje cell inhibition on their target neurones, which increases during the initial period, gradually diminishes during the adaptation time, and then stabilizes to a subnormal state.

Aging↗

PubMed1985

Release of cerebellar inhibition by climbing fiber deafferentation.

Cerebellar units were recorded extracellularly in rats before and after an intraveinous injection of 3-acetylpyridine destroying selectively the IO. All the Purkinje cells show a loss of the complex discharge between 2 h 15 min and 2 h 45 min after treatment. This time, called the "critical period" corresponds to the degeneration of the neurons of the inferior olive as revealed by the decrease of their metabolic activity. The simple spikes of the Purkinje cells increase their discharge frequency soon after the climbing fibers cease firing. On the contrary the firing frequency of the inhibitory interneurons does not show significant changes after degeneration of the inferior olive. The efferent cerebellar neurons, including cells of the cerebellar and vestibular nuclei receiving the axon terminals of the Purkinje cells, decrease their discharge rate up to thirty times during and after the critical period. It is demonstrated that this effect is due to the increased inhibitory activity of the Purkinje cells deafferented from the climbing fibers, whereas the deafferentation of the efferent cerebellar neurones from the collaterals of the olivary cells has little impact.

Animals↗

PubMed1985

[Activity of neurons of the red nucleus after destruction of the inferior olive in the rat].

The spontaneous frequency of discharge of the red nucleus neurones has been evaluated in the rat before and after total and bilateral destruction of the inferior olive by 3-acetylpyridine. The suppression of the inferior olive increasing the cerebellar inhibition, produces, as a consequence, a consequence, a disfacilitation of the activity of the red nucleus neurones. The process persists for a few days, then a progressive compensation takes place. A month later the average frequency of discharge is recovered but a normal unit activity and motor behaviour are not restaured.

Animals↗

PubMed1984

[Depression of the efferent activity of the cerebellar nuclei following destruction of the inferior olive].

The spontaneous discharge frequency of the fastigial and interpositus nuclei was evaluated in three experimental conditions in Rat: (a) in the "intact" animal; (b) in animals with total and selective destruction of the inferior olive, depriving the Purkinje cells of their afferent climbing fiber; (c) in animals having inferior olive destruction and cryocoagulation of the cerebellar cortex, destroying Purkinje cells innervating the neurones of the fastigial and interpositus nuclei. Unit activity was high in group (a) (32.9 +/- 22.9/s); it was markedly reduced in group (b) (1.1 +/- 1.3/s); it was higher in group (c) than in group (a) (43.7 +/- 25.5/s). Suppression of the inferior olive thus increases the Purkinje cell inhibitory action upon neurones of the cerebellar nuclei.

Animals↗

PubMed1984

[Long-term changes in the activity of Purkinje cells and efferent cerebellar neurons following bilateral destruction of the inferior olive].

The spontaneous discharge frequency of Purkinje cells and neurones of the cerebellar nuclei was evaluated in rats after complete bilateral destruction of their inferior olive with 3-acetylpyridine, performed one day to six months before. The deafferentation from the climbing fibers produced an increased inhibitory action of the Purkinje cells on their target neurones, lasting at least for one week. A relative compensation took place progressively during the first month, but the normal activity of the circuit did not recover even after six months.

Animals↗