Basal forebrain cholinergic neurons are selectively vulnerable to AMPA/kainate receptor-mediated neurotoxicity.

We exposed murine basal forebrain neuronal cultures for 24 h to defined concentrations of N-methyl-D-aspartate, kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and assessed the resultant degeneration of the cholinergic neuronal subpopulation, as identified by choline acetyltransferase immunocytochemistry and acetylcholinesterase histochemistry. Cholinergic neurons, representing about 0.5% of the total neuronal population, were atypically vulnerable to excitotoxins. Compared to most basal forebrain neurons, they were more vulnerable to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor-mediated injury and slightly less vulnerable to N-methyl-D-aspartate receptor-mediated injury. The present findings provide quantitative demonstration of a mechanism that preferentially injures basal forebrain cholinergic neurons, and may thus suggest candidate factors pertaining to their loss in disease states like Alzheimer's disease.