Cholinergic Mechanisms in Generalized Seizures: Importance of the Zona Incerta

Abstract

AbstractObjective:Stimulation of the central cholinergic system results in generalized epileptic seizures. The goal of this study was to map the epileptogenic effects of the cholinergic agonist, carbachol injected into different sites of the basal forebrain and diencephalon of the rat brain.Methods:Carbachol was injected directly into the brain in a dose of 1 or 3 (jg. Seizures were assessed behaviourally on a five-stage scale with electroencephalographic controls. Seizures at stage 1 were the least severe and those at stage 5 the most severe.Results:Injections of high dose carbachol (3 (jg) induced seizures from 40% of all injected brain sites. Injections of low dose carbachol (1 ug) or isotonic saline into the same brain sites did not cause any behavioural or electrographic seizures. The majority of sites (84%) producing generalized seizures (stage 5) were concentrated in or around the zona incerta.Conclusions:Within the anatomical limits of the study, the zona incerta is the area most sensitive to carbachol-induced generalized seizures.