Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity

Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP expression in the damaged MBN are still elusive. Hence, we performed multiple-labeling immunocytochemistry for choline-acetyltransferase (ChAT), neuron-specific nuclear protein (NeuN) and APP 4, 24, and 48 h after NMDA infusion in the MBN. Whereas all cholinergic neurons were immunoreactive for NeuN, this neuronal marker also labeled a population of ChAT-immunonegative non-cholinergic neurons. Both neuron populations exhibited a similar degree of sensitivity to NMDA excitotoxicity that became evident as early as 4 h post-lesion. Cholinergic MBN neurons showed abundant APP immunoreactivity (approximately 90%), while only a fraction (approximately 20-30%) of non-cholinergic neurons expressed the protein. Remarkably, cholinergic but not non-cholinergic neurons retained their APP immunoreactivity after NMDA infusion. In conclusion, cholinergic MBN neurons are not preferentially sensitive to short-term excitotoxicity, but are one of the major sources of APP in the basal forebrain.