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M Vergnes

Publications and source records attributed to M Vergnes.

At least 19 recordsLinked to original sources
PubMed1997

The amygdala is critical for seizure propagation from brainstem to forebrain.

Audiogenic seizures, a model of brainstem epilepsy, are characterized by a tonic phase (sustained muscular contraction fixing the limbs in a flexed or extended position) associated with a short cortical electroencephalogram flattening. When sound-susceptible rats are exposed to repeated acoustic stimulations, kindled audiogenic seizures, characterized by a clonic phase (facial and forelimb repetitive jerks) associated with cortical spike-waves, progressively appear, suggesting that repetition of brainstem seizures causes a propagation of the epileptic discharge toward the forebrain. In order to determine the structures through which this propagation occurs, four kinds of experiments were performed in non-epileptic rats and in sound-susceptible rats exposed to single or repeated sound stimulations. The following results were obtained: (I) Electrical amygdalar kindling was similar in non-epileptic and naive-susceptible rats, but was facilitated in sound-susceptible rats submitted to 40 acoustic stimulations and presenting kindled audiogenic seizures. (2) Audiogenic seizures induced an increase in [(14)C]2-deoxyglucose concentration in the amygdala after a single seizure, and in the amygdala, hippocampus and perirhinal and piriform cortices after a kindled audiogenic seizure. (3) A single audiogenic seizure induced the expression of c-Fos protein mainly in the auditory nuclei. A few cells were stained in the amygdala. After 5-10 audiogenic seizures, a clear staining appeared in the amygdala, and perirhinal and piriform cortices. The hippocampus expressed c-Fos later, after 40 audiogenic seizures. (4) Injection of lidocaine into the amygdala did not modify single audiogenic seizures, but suppressed myoclonias and cortical spike-waves of kindled audiogenic seizures. Similar deactivation of the hippocampus failed to modify kindled audiogenic seizures. Taken together, these data indicate a critical role for the amygdala in the spread of audiogenic seizures from brainstem to forebrain.

Acoustic Stimulation↗
PubMed1997

Involvement of proprioceptive feedback in brainstem-triggered convulsions.

PURPOSE: In rodents, specific motor components of generalized convulsive seizures depend on two distinct anatomic substrates: (a) forebrain networks are responsible for facial and forelimb clonus with or without rearing and falling; and (b) brainstem networks are responsible for running-bouncing fits and tonic convulsions. To investigate the requirement of proprioceptive inputs in the generation of these two different types of seizures, we compared the effects of neuromuscular blockade by D-tubocurarine on the EEG expression of brainstem- and forebrain-triggered seizures. METHODS: Unilateral electrical stimulations were applied for 50 consecutive days in freely moving male adult rats through a bipolar electrode aimed at the dorsal hippocampus (n = 5), the occipital cortex (n = 4), the inferior colliculus (n = 6), or the midbrain reticular formation (n = 6). Two days after the last stimulation, rats were paralyzed with d-tubocurarine and stimulated in the same way. RESULTS: In brainstem structures, the first electrical stimulation induced tonic seizures concomitant with low-voltage cortical activity; repetition of daily stimulations progressively induced tonic-clonic seizures associated with high-amplitude cortical spike-wave discharges. After immobilization by d-tubocurarine, brainstem stimulations failed to induce any EEG paroxysm. In forebrain structures, repeated electrical stimulations produced a classic kindling with progressive occurrence of clonic seizures associated with large cortical discharges; d-tubocurarine left unchanged the EEG pattern of these latter seizures. CONCLUSIONS: These data suggest that proprioceptive reafferentation resulting from movement is necessary for the generation of self-sustained brainstem seizures but is not implicated in the elaboration of forebrain seizures.

Animals↗
PubMed1996

Interictal cerebral metabolic levels in Wistar rats sensitive to audiogenic seizures.

In the present study, we compared interictal local cerebral metabolic rates for glucose (LCMRglcs) in a strain of audiogenic rats (Wistar AS) selected in our laboratory to interictal LCMRglcs in a strain of control non-epileptic (NE) rats. Two groups of Wistar AS were studied, one group exposed to a single audiogenic seizure and one group of kindled rats exposed to 40 daily repetitive seizures. Control NE animals were exposed to a single sound exposure which did not induce any behavioral disturbance. Interictal LCMRglcs were measured by the quantitative autoradiographic [14C]2-deoxyglucose technique 5 days after the last sound exposure. LCMRglcs were similar in the three groups of rats in 80% of the structures. Compared to the control NE strain, interictal metabolic levels were mainly decreased in auditory structures of Wistar AS, either naive or kindled, thus confirming auditory impairment in audiogenic animals. LCMRglcs were increased over control levels in both groups of Wistar AS in cerebellar regions. This increase of cerebellar functional activity in Wistar AS compared to control NE rats might reflect an increased cerebellar input which, together with auditory impairment, may facilitate the induction of seizure activity in Wistar AS. Finally, there was no difference between the interictal cerebral metabolic level of naive and kindled Wistar AS, except in the cerebellar dentate nucleus where LCMRglc was significantly higher in kindled than in naive animals.

Acoustic Stimulation↗
PubMed1996

Thalamic NMDA transmission in a genetic model of absence epilepsy in rats.

In the selected strain of GAERS Wistar rats (Genétic Absence Epilepsy Rats from Strasbourg), all animals present spontaneously recurrent absence seizures characterized by bilateral and synchronous generalized spike-and-wave discharges (SWD) accompanied by behavioural arrest. SWD depend on a thalamo-cortical network connecting the reticular and relay nuclei of the thalamus and their cortical projection areas. This loop involves both GABAergic and glutamatergic synapses. In the present study, we investigated the implication of NMDA transmission in the genesis of absence seizures in GAERS. Intra-peritoneal or intra-cerebroventricular injections of NMDA, the competitive NMDA antagonist CGP 40116, the non-competitive NMDA antagonist (+)-MK 801 and the antagonist of the glycine modulatory site 5,7-dichlorokynurenic acid dose-dependently suppressed SWD. Bilateral infusions of the same drugs in the lateral relay nuclei of the thalamus had similar suppressive effects. Intra-cerebroventricular or intrathalamic administration of D-serine, an agonist of the glycine modulatory site, had no effect on SWD. These data show that NMDA neurotransmission, especially within the thalamus, plays a major role in the control of absence seizures in GAERs. Disregulation of NMDA-mediated transmission by NMDA or antagonists, interacting with various sites of the receptor complex, may suppress the thalamo-cortical oscillatory activity which underlies SWD.

Animals↗
PubMed1996

Absence seizures induce a decrease in cerebral blood flow: human and animal data.

Our previous studies on cerebral metabolic activity in genetic absence epilepsy rats from Strasbourg (GAERS) were in favor of decreased functional activity during absences and normal or increased interictal activity. To ascertain that hypothesis, in the present study we performed continuous measurements of CBF in both children with typical absence epilepsy and GAERS, using Doppler ultrasonography and laser-Doppler flowmetry, respectively. CBF fluctuations during absences were recorded in four children between 5 and 6 years of age and 16 adult GAERS. In both children and animals, CBF measured in the middle cerebral artery and cortical capillaries, respectively, significantly decreased by a median value of 20-24% under basal levels during spontaneous absences. In GAERS, CBF levels were continuously decreased during haloperidol-induced absence status epilepticus, while they were not affected by ethosuximide. Conversely, convulsive seizures induced in rats either by kainate or picrotoxin led to a 175-664% increase in CBF levels. In conclusion, the present data show that during spontaneous absences, CBF decreases under basal levels in both cortical capillaries (GAERS) and the middle cerebral artery (children). Moreover, these fluctuations occur in vessels with normal vascular reactivity, are not mediated by changes in PO2, PCO2, or arterial blood pressure, and represent rather a response to reduced metabolic demand.

Animals↗
PubMed1995

Mesopontine cholinergic control over generalized non-convulsive seizures in a genetic model of absence epilepsy in the rat.

Pharmacological data have shown that the cholinergic transmission participates in the control of spike-and-wave discharges in rats with genetic absence epilepsy. The corticothalamic circuitry which generates spontaneous spike-and-wave discharges, the electroencephalographic expression of absence seizures, receives important cholinergic inputs from two distinct sources: (i) the nucleus basalis projecting mainly to the cortex and (ii) the pedunculopontine and laterodorsal tegmental nuclei providing cholinergic afferents to the thalamus. In the present study, the involvement of the cholinergic mesopontothalamic projections in the control of spike-and-wave discharges was investigated. Activation of cell bodies in the pedunculopontine and laterodorsal tegmental nuclei, by local microinjections of non-toxic doses of kainate (20 pmol/side) or picrotoxin (66 pmol/side), suppressed spike-and-wave discharges. Similar effects were produced by direct cholinergic activation of the ventrolateral part of the thalamus: intrathalamic microinjections of carbachol (0.7-2.8 pmol/side), a cholinergic receptor agonist, resulted in a dose-dependent suppression of spike-and-wave discharges. This suppression was partially reversed by a simultaneous microinjection of an equimolar dose of scopolamine, a muscarinic receptor antagonist. Electrolytic or neuroexcitotoxic lesions of the pedunculopontine and laterodorsal tegmental nuclei did not modify spike-and-wave discharges. These results suggest that the cholinergic mesopontine projection to the thalamus exerts a phasic inhibitory control of generalized non-convulsive epileptic seizures.

Animals↗
PubMed1995

Mapping of cerebral blood flow changes during audiogenic seizures in Wistar rats: effect of kindling.

The quantitative autoradiographic [14C]iodoantipyrine technique was applied to the measurement of rates of local cerebral blood flow (LCBF) during audiogenic seizures in Wistar AS rats belonging to a genetic strain selected at the Centre de Neurochimie (Strasbourg, France) for their sensitivity to sound. Seizures were elicited in native rats never exposed to sound (single audiogenic seizures) or in rats previously exposed to 10-40 seizure-inducing sound stimulations until generalization of the seizure to forebrain areas (referred to as "kindled animals"). During single audiogenic seizures, rates of LCBF increased over control values in all areas but the genu of the corpus callosum. The highest increases in LCBF (180-388%) were recorded in the inferior and superior colliculus, reticular formation, monoaminergic cell groupings, especially the substantia nigra, posterior vegetative nuclei, and many thalamic and hypothalamic regions. The lowest increases were seen in forebrain limbic regions and cortical areas. In kindled animals, LCBF rates increased over control levels in 67 areas of the 75 studied. LCBF increases were generally of a lower amplitude in kindled than in naive rats. Differences between the two groups of seizing rats were located mostly in brain-stem regions, mainly the inferior colliculus, reticular formation, substantia nigra, and posterior vegetative nuclei. Conversely, rates of LCBF were similar in forebrain areas of naive and kindled animals. In conclusion, the present data show that there is a good correlation between the structures known to be involved in the expression of audiogenic seizures (inferior colliculus, reticular formation, substantia nigra mainly) and the large increase in LCBF during single audiogenic seizures, while rates of LCBF increase to a lesser extent in forebrain areas not involved in this type of seizures. The circulatory adaptation to kindled seizures is rather a decreased response in brain-stem regions and no change in the forebrain, although the kindling process induces a generalization of the seizure from brain-stem to anterior regions.

Acoustic Stimulation↗
PubMed1994

C-fos expression after single and kindled audiogenic seizures in Wistar rats.

In naive Wistar rats susceptible to sound, a single audiogenic seizure induced the expression of c-fos in the subcortical auditory nuclei whereas the forebrain was almost completely devoid of any labelling. After kindling of audiogenic seizures by 40 daily exposures to sound, the seizure induced a strong c-fos expression in the amygdala, the piriform cortex, the hippocampus and the neocortex. These results confirm: (1) that audiogenic seizures are brain-stem seizures related to dysfunction of auditory pathways, and (ii) that kindling of audiogenic seizures recruits forebrain and limbic structures into the seizure network.

Acoustic Stimulation↗
PubMed1994

Nucleus basalis lesions suppress spike and wave discharges in rats with spontaneous absence-epilepsy.

Cholinergic drugs were shown to affect spike and wave discharges in a selected strain of Wistar rats with generalized non-convulsive absence epilepsy, named GAERS (Genetic Absence Epilepsy Rats from Strasbourg). The involvement of cholinergic transmission from the nucleus basalis in the control of absence seizures in GAERS was investigated in the present study, by examining the effects of unilateral excitotoxic lesions of this nucleus on the occurrence of spike-wave discharges. Ibotenate (0.01 M) and quisqualate (0.03 and 0.06 M)-induced lesions of the nucleus basalis suppressed spike-wave discharges in the cortex ipsilateral to the lesion. The suppression was associated with a disappearance of both acetylcholinesterase-fibres in the cerebral cortex and choline acetyltransferase immunopositive neurons within the nucleus basalis. Concomitantly, the background electroencephalographic activity was slowed. These results suggest that cholinergic innervation of the cerebral cortex by the nucleus basalis is involved in the occurrence of generalized non-convulsive seizures, in relation to the control of cortical activation.

Acetylcholinesterase↗
PubMed1993

Thalamic low threshold calcium current in a genetic model of absence epilepsy.

The low threshold calcium current (IT) in thalamo-cortical neurones contributes to the generation of spike and wave discharges (SWDs) characteristic of generalized, non-convulsive absence epilepsy. The biophysical properties of this current were analysed in dorsal lateral geniculate neurones from the Genetic Absence Epilepsy Rats from Strasbourg (GAERS+). No difference was found in the voltage dependence and kinetics of IT between GAERS+ and rats of the non epileptic control strain (GAERS-). Thus, a dysfunction of IT does not appear to underlie the occurrence of SWDs in absence epilepsy.

Animals↗
PubMed1993

Cerebral energy metabolism in rats with genetic absence epilepsy is not correlated with the pharmacological increase or suppression of spike-wave discharges.

The quantitative [14C]2-deoxyglucose (2-DG) autoradiographic method was applied to measure the effects of pharmacological agents on local cerebral metabolic rates of glucose (LCMRglcs) in a selected strain of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). In a previous study, we have shown that GAERS display an overall significant increase of LCMRglc compared to non-epileptic rats from a selected strain. To further characterize the metabolic responses in GAERS, we measured the effects of drugs aggravating or suppressing absences. The animals were divided into 4 groups, i.e. 2 non-epileptic control groups and 2 GAERS groups. Ten min before the initiation of the 2-DG procedure, both non-epileptic control and epileptic rats received an injection of the same amount of the pharmacological agent, either haloperidol (2 mg/kg) or ethosuximide (200 mg/kg). In the presence of haloperidol, GAERS exhibited almost continuous spike-wave discharges; however, the difference in energy metabolism between GAERS and non-epileptic control rats was abolished and LCMRglcs were similar in all structures of both groups of animals. In GAERS treated with ethosuximide, spike-wave discharges were totally suppressed, whereas rates of energy metabolism remained higher by 31-72% in all structures of epileptic rats compared to their corresponding non-epileptic controls. These data demonstrate a lack of correlation between the occurrence of spike-wave discharges and LCMRglcs and are in favor of normal or decreased ictal metabolism and of increased interictal glucose utilization by the brain in rats with absence epilepsy.

Action Potentials↗
PubMed1993

Effects of cholinergic drugs on genetic absence seizures in rats.

Wistar rats of a selected strain show spontaneous generalized non-convulsive seizures with bilateral synchronous spike-wave discharges on the cortical electroencephalograph (EEG). The 7 to 9 c/s spike-wave discharges occur predominantly in waking states of inactivity. The effects of cholinergic drugs on the cumulated duration of spike-wave discharges were investigated in this rat model of absence epilepsy. I.p. injections of drugs which potentiate cholinergic neurotransmission, namely the acetylcholinesterase inhibitor, physostigmine (0.1-0.5 mg/kg), the muscarinic receptor agonists, oxotremorine (0.25-1 mg/kg) and pilocarpine (0.125-2 mg/kg), and the nicotinic receptor agonist, nicotine (0.062-2 mg/kg), suppressed discharges in a dose-dependent manner and induced an arousal-like cortical EEG. The muscarinic receptor antagonist, scopolamine, increased the spike-wave discharges at doses below 0.05 mg/kg; at higher doses (0.05-1 mg/kg) it decreased discharges and induced a sleep-like EEG. The nicotinic receptor antagonist, mecamylamine (0.5-6 mg/kg), had no effect on spike-wave discharges or the EEG. These results suggest that cholinergic activity accounts for the preferential occurrence of absence seizures in states of reduced arousal.

Animals↗
PubMed1993

22-28 kHz ultrasonic vocalizations associated with defensive reactions in male rats do not result from fear or aversion.

This study was carried out to determine whether 22-28 kHz vocalizations emitted during intermale interactions in adult rats were related with a state of fear, aversion or resulted from painful stimulation. Vocalizations in the 22-28 kHz range were measured in male rats during non-aggressive and aggressive social interactions; when given foot shock with a partner; during non-aggressive social interactions after an injection of (i) acetic acid (1%, IP); (ii) pentylenetetrazol (20-30 mg/kg, IP) and (iii) lithium chloride (63.8 mg/kg, IP). Ultrasonic vocalizations were consistantly detected in all rats while the animals displayed defensive or submissive postures when tested as intruders confronted with offensive residents or when administered foot shocks. Only occasional vocalizations were emitted, even in the presence of a partner, when the animals had received other painful or aversive treatments. These data support the hypothesis that 22-28 kHz vocalizations during intermale interactions are associated with defensive postures and are not the consequence of a state of fear or aversion.

Acetates↗
PubMed1993

GABAA receptor impairment in the genetic absence epilepsy rats from Strasbourg (GAERS): an immunocytochemical and receptor binding autoradiographic study.

Some aspects of the GABA and cholinergic systems have been investigated in the cortex and thalamus of GAERS Wistar rats, a model of petit-mal epilepsy, and in a non-epileptic control strain. GABA and its synthetic enzyme, glutamic acid decarboxylase (GAD), were located by immunocytochemistry; the GABAA receptors were evaluated by autoradiography of GABA-enhanced 3H-flunitrazepam binding and by immunocytochemistry using specific antibodies against the beta 2-beta 3 subunits of GABAA receptor protein. GABA and GAD immunocytochemistry did not show up any difference in density or distribution of immunoreactive elements (fibers, terminals and neurons) between epileptic and control animals, but autoradiographic and immunocytochemical studies showed a decreased enhancement of 3H-flunitrazepam binding and of beta 2-beta 3 subunits of GABAA receptor in the sensorimotor cortex and anterior thalamic areas of the epileptic strain. No differences were found in benzodiazepine receptors in the two strains. GABAB receptors were measured as 3H-baclofen binding in a crude synaptic membrane preparation and there was no difference between epileptic and control animals. Choline acetyltransferase, the synthetic enzyme for acetylcholine, and muscarinic receptor subtypes (M1 and M2), visualized respectively by an immunocytochemical procedure and binding autoradiography, did not differ in epileptic and normal rats. The data suggest an impairment of the 'GABAA system' in restricted brain regions of epileptic rats, due to a reduction of receptor beta 2-beta 3 subunits and coupling to benzodiazepine receptors despite the normal synthesis and location of the neurotransmitter.

Acetylcholine↗
PubMed1993

Reciprocal positive transfer between kindling of audiogenic seizures and electrical kindling of inferior colliculus.

The behavioral and EEG concomitants of kindling produced by daily electrical stimulation of the inferior colliculus have been recorded in three series of Wistar rats: (1) non epileptic controls (NE), (2) rats susceptible to audiogenic seizures (AS), (3) acoustically susceptible rats with prior kindling of audiogenic seizures by repeated sound exposure (KAS). Repeated collicular stimulation produced behavioral and EEG changes which were similar in the AS and the NE rats. The tonic seizure without cortical discharges elicited by the first stimulation progressively changed into tonic-clonic seizures with sustained cortical EEG discharges after more than 20 stimulations. In the KAS group, the electrical collicular kindling was clearly accelerated: kindled tonic-clonic seizures and their EEG discharges already occurred after one to five electrical stimulations. Similarly, after completion of electrical collicular kindling in AS, sound stimulations immediately induced characteristic kindled audiogenic seizures. The immediate reciprocal positive transfer observed between kindling of audiogenic seizures and kindling of seizures induced by electrical stimulation of the inferior colliculus suggests that kindling of these two brain-stem seizures involves similar structures and mechanisms.

Acoustic Stimulation↗
PubMed1992

The GABAA receptor complex in experimental absence seizures in rat: an autoradiographic study.

The regional distribution of radioactive ligand binding for different receptors of the gamma-aminobutyric acid A (GABAA)-benzodiazepine-picrotoxin chloride channel complex was measured on tissue section by autoradiography in brains taken from a genetic strain of Wistar rats with spontaneous absence-like seizures, the genetic absence epilepsy rats from Strasbourg (GAERS), and a control colony. The ligands employed included [3H]muscimol for high affinity GABA agonists sites; [3H]SR 95531 for the low-affinity GABA sites; [3H]flunitrazepam for the benzodiazepine sites; and [35S]t-butyl bicyclophosphorothionate (TBPS) for the picrotoxin site. There was no significant change between GAERS and control animals in [3H]flunitrazepam and [35S]TBPS binding. However, there was significantly decreased [3H]muscimol and [3H]SR 95531 binding in the CA2 region of the hippocampus of the GAERS. This was due to a decrease in Bmax of both [3H]muscimol and [3H]SR 95531 binding in the epileptic strain.

Animals↗
PubMed1992

Dorsal tegmentum kindling in rats.

Electrical stimulations were applied daily for 40 days to the dorsal tegmentum in 9 rats through chronically implanted bipolar electrodes. The intensity of current (2 s trains of 50 Hz, 1 ms monophasic square waves) necessary to trigger a full tonic seizure was determined and applied for all further stimulations. Initial stimulations induced a tonic seizure with a low voltage fast electrocorticographic activity. After repeated stimulations, high amplitude spike and wave discharges developed over the cortex, their duration exceeding 50 s at the 40th stimulation. Simultaneously, the tonic seizures evolved into tonic-clonic fits with bilateral myoclonias following the tonic phase. These EEG and behavioral modifications persisted for 30 days after the last stimulus. These results demonstrate that kindling may be obtained from brainstem structures.

Animals↗