BASAL FOREBRAIN CHOLINERGIC NEURONS ARE SELECTIVELY VULNERABLE TO AMPA KAINATE RECEPTOR-MEDIATED NEUROTOXICITY/

We exposed murine basal forebrain neuronal cultures for 24 h to define d concentrations of N-methyl-D-aspartate, kainate or pha-amino-3-hydro xy-5-melhyl-4-isoxazolepropionate and assessed the resultant degenerat ion of the cholinergic neuronal subpopulation, as identified by cholin e acetyltransferase immunocytochemistry and acetylcholinesterase histo chemistry. Cholinergic neurons, representing about 0.5% of the total n euronal population, were atypically vulnerable to excitotoxins. Compar ed to most basal forebrain neurons, they were more vulnerable to o-3-h ydroxy-5-methyl-4-isoxazolepropionate/kainate receptor-mediated injury and slightly less vulnerable to N-methyl-D-aspartate receptor-mediate d injury. The present findings provide quantitative demonstration of a mechanism that preferentially injures basal forebrain cholinergic neu rons, and may thus suggest candidate factors pertaining to their loss in disease states like Alzheimer's disease.