The role of the basal forebrain cholinergic system in pathogenesis of genetically determined absence epilepsy

Abstract

The role of cholinergic innervations of reticular thalamic nucleus and nucleus basalis of Meynert in mechanisms of spontaneous spike-and-wave discharges (SWDs) generation was investigated in the WAG/Rij rat model of absence epilepsy. For selective lesions of cholinergic cell bodies and terminals cholinotoxin AF64A was used. AF64A was administered i.c.v. bilaterally (3 nmol/side) or unilaterally (1 nmol) to the rostral pole of reticular thalamic nucleus. Both injections caused a decrease in number and mean duration of the SWDs in frontal cortex EEG either on the ipsilateral or contralateral side of the lesion. The number of the normal sleep spindles was also reduced after the lesion. The lesioned hemisphere revealed changes in the spectral content of SWDs and sleep spindles after the administration of AF64A. Histological (immunohistochemistry) verification showed a loss of ChaT-immunoreactive neurons at the side of the lesion in the region of nucleus basalis of Meynert and globus pallidus. It can be concluded that the loss of cholinergic innervation from nucleus basalis lead to the abolition of both normal spindles and paroxysmal SWDs. This fact points on the possible similarities in the mechanisms of generation of these two phenomena of cortical synchronized activity. Nucleus basalis is known as the major source of cholinergic cortical afferentation and plays an important role in the control of arousal. It is assumed that certain level of neocortical excitability provided by cholinergic input from nucleus basalis of Meynert is necessary for the generation of spontaneous SWDs and normal sleep spindles in WAG/Rij rats.