Survival of Cholinergic Forebrain Neurons in Developing p75$^{NGFR}$- Deficient Mice

The functions of the low-affinity p75 nerve growth factor receptor (p75$^{NGFR}$) in the central nervous system were explored in vivo. In normal mice, approximately 25 percent of the cholinergic basal forebrain neurons did not express TrkA and died between postnaatl day 6 and 15. This loss did not occur in p75$^{NGFR}$-deficient mice or in normal mice systemically injected with a p75$^{NGFR}$-inhibiting peptide. Control, but not p75$^{NGFR}$-deficient, mice also had fewer cholinergic striatal interneurons. Apparently, p75$^{NGFR}$ mediates apoptosis of these developing neurons in the absence of TrkA, and modulation of p75$^{NGFR}$ can promote neuronal survival. Cholinergic basal forebrain neurons are involved in learning and memory.