The inhibitory control of the substantia nigra over generalized non-convulsive seizures in the rat.
A system exerting inhibitory control over generalized epilepsies and involving neurons from the substantia nigra has been described by several authors in experimental models of convulsive seizures. In the present study, the existence of such a control system governing absence epilepsy was investigated using models of non-convulsive seizures in the rat. Activation of the GABAergic neurotransmission within the substantia nigra by local injection of GABA agonists (muscimol, THIP) or an inhibitor of GABA degradation (gamma-vinyl GABA) suppresses generalized non convulsive seizures, whether they are genetically determined or induced by systemic injections of gamma-butyrolactone (100 and 200 mg/kg), pentylenetetrazole (20 mg/kg) or THIP (7.5 mg/kg). The ascending dopaminergic nigral output or the GABAergic fibres to the ventromedial thalamus are not critically involved in this control system. By contrast, the GABAergic nigro-collicular pathway appears crucial: bilateral lesion of the superior colliculus abolishes the anti-epileptic effects of intranigral injection of muscimol and blockade of the GABAergic transmission within the superior colliculus results in a suppression of generalized non-convulsive seizures. Finally, activation of collicular cell bodies by low doses of kainic acid significantly suppresses absence seizures. These results suggest the existence of a control system inhibiting generalized non-convulsive seizures which is activated by the release of the tonic inhibition exerted by the nigral GABAergic fibres on collicular neurons. The similarities between this system and the control system described for convulsive seizures are discussed.
Depaulis
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Laboratoire de Neurophysiologie et Biologie des Comportements, Centre de Neurochimie du CNRS, Strasbourg, France.
D000818:Animals; D001931:Brain Mapping / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D004832:Epilepsy, Absence / Q000503:physiopathology*; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D013378:Substantia Nigra / Q000503:physiopathology*; D013477:Superior Colliculi / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D013788:Thalamus / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D004298:Dopamine