ABSENCE OF P75(NTR) CAUSES INCREASED BASAL FOREBRAIN CHOLINERGIC NEURON SIZE, CHOLINE-ACETYLTRANSFERASE ACTIVITY, AND TARGET INNERVATION

Emerging evidence suggests that the p75 neurotrophin receptor (p75(NTR )) mediates cell death; however, it is not known whether p75(NTR) nega tively regulates other neuronal phenotypes. We found that mice null fo r p75(NTR) displayed highly significant increases in the size of basal forebrain cholinergic neurons, including those that are TrkA-positive . Cholinergic hippocampal target innervation also was increased signif icantly. Activity of the cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) was increased in both the medial sep tum and hippocampus. Upregulation of these cholinergic features was no t associated with increased basal forebrain or hippocampal target NGF levels. In contrast, striatal cholinergic neurons, which do not expres s p75(NTR), showed no difference in neuronal number, size, or ChAT act ivity between wild-type and p75(NTR) null mutant mice. These findings indicate that p75(NTR) negatively regulates cholinergic neuronal pheno type of the basal forebrain cholinergic neurons, including cell size, target innervation, and neurotransmitter synthesis.