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) negatively regulates other neuronal phenotypes. We found that mice null for 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 significantly. Activity of the cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (CHAT) was increased in both the medial septum and hippocampus. Upregulation of these cholinergic features was not associated with increased basal forebrain or hippocampal target NGF levels. In contrast, striatal cholinergic neurons, which do not express p75(NTR), showed no difference in neuronal number, size, or ChAT activity between wild-type and p75(NTR) null mutant mice. These findings indicate that p75(NTR) negatively regulates cholinergic neuronal phenotype of the basal forebrain cholinergic neurons, including cell size, target innervation, and neurotransmitter synthesis.