MESOPONTINE CHOLINERGIC CONTROL OVER GENERALIZED NONCONVULSIVE SEIZURES IN A GENETIC MODEL OF ABSENCE EPILEPSY IN THE RAT

Pharmacological data have shown that the cholinergic transmission part icipates in the control of spike-and-wave discharges in rats with gene tic absence epilepsy. The corticothalamic circuitry which generates sp ontaneous spike-and-wave discharges, the electroencephalographic expre ssion 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 nucle i providing cholinergic afferents to the thalamus. In the present stud y, 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 nuc lei, by local microinjections of non-toxic doses of kainate (20 pmol/s ide) or picrotoxin (66 pmol/side), suppressed spike-and-wave discharge s. Similar effects were produced by direct cholinergic activation of t he ventrolateral part of the thalamus: intrathalamic microinjections o f carbachol (0.7-2.8 pmol/side), a cholinergic receptor agonist, resul ted in a dose-dependent suppression of spike-and-wave discharges. This suppression was partially reversed by a simultaneous microinjection o f an equimolar dose of scopolamine, a muscarinic receptor antagonist. Electrolytic or neuroexcitotoxic lesions of the pedunculopontine and l aterodorsal 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-con vulsive epileptic seizures.