Excitotoxic lesions of rat basal forebrain: Differential effects on choline acetyltransferase in the cortex and amygdala

Abstract

Previous studies have shown that basal forebrain lesions using different excitotoxins produce similar decreases in cortical choline acetyltransferase, but differential effects on memory. However, basal forebrain cholinergic neurons send efferents to the amygdala and cortex. The present studies compared the effects of several excitotoxins on choline acetyltransferase levels in both of these structures. Lesions of the basal forebrain were made in rats by infusing different doses of either α-amine-3-hydroxy-5-methyl-4-isoxazole propionic acid, ibotenic acid, quisqualic acid, quinolinic acid or N- methyl- d-aspartic acid and measuring choline acetyltransferase seven days later. All of the excitotoxins exerted a differential response on cholinergic neurons of the basal forebrain projecting to the cortex or amygdala. Quinolinic acid was a more potent neurotoxin to cholinergic neurons innervating the amygdala than those projecting to the cortex. In contrast, quisqualic acid and α-amine-3-hydroxy-5-methyl-4-isoxazole were more potent neurotoxins to the cortical projection. α-Amine-3-hydroxy-5-methyl-4-isozazole propionic acid was the most potent excitotoxin for destroying cholinergic neurons innervating either the cortex or amygdala. A parallel neurotoxic response was obtained in the cortex and amygdala following infusion of ibotenic acid or N- methyl- d-aspartic acid with little selectivity for choline acetyltransferase depletion in the cortex or amygdala. Histological analysis of the injection site revealed that acetylcholinesterase-positive neurons were destroyed by the excitotoxins in a dose-dependent manner. Excitotoxins (ibotenic acid, quinolinic acid, N- methyl- d-aspartic acid) that produce the greatest impairments in memory were found to produce the greatest depletion of choline acetyltransferase in the amygdala. These results might suggest that cholinergic neurons projecting to the amygdala play an important role in memory.