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.