Effects of selective toxic lesions of cholinergic neurons of the laterodorsal tegmental nucleus on experimental seizures

This study determined the effects of bilateral discrete partial lesions of cholinergic neurons of the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum on seizures induced by intravenous pentylenetetrazol (PTZ). Relatively selective lesions produced by bilateral 50 nl microinjections of 75 pmol of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) resulted in a significant reduction in the threshold of myoclonic and facial-forelimb clonic seizures but not tonic seizures when PTZ was infused 7 days later. This demonstrates that this cholinergic nucleus is a key site of subcortical seizure regulation. We propose that this control is mediated by ascending projections from the LDTg to the central medial intralaminar nucleus of the thalamus.