Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats

Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hi ppocampus and cortical areas, and to facilitate seizure development in hipp ocampal kindling. Here we demonstrate that this lesion also accelerates sei zure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated th e development of the initial stages of hippocampal kindling, the same lesio n promoted the late stages of amygdala kindling. To explore the role of var ious parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or c ortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respec tively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more wides pread lesion induced by intraventricular 192 IgG-saporin. In contrast, remo val of the cholinergic input to the hippocampus had no effect on the develo pment of amygdala kindling. These data indicate that basal forebrain cholin ergic neurons suppress kindling elicited from amygdala, and that this dampe ning effect is mediated via cortical but not hippocampal projections.