SURVIVAL OF CHOLINERGIC FOREBRAIN NEURONS IN DEVELOPING P75(NGFR)-DEFICIENT MICE

The functions of the low-affinity p75 nerve growth factor receptor (p7 5(NGFR)) in the central nervous system were explored in vivo. In norma l mice, approximately 25 percent of the cholinergic basal forebrain ne urons did not express TrkA and died between postnatal day 6 and 15. Th is loss did not occur in p75(NGFR)-deficient mice or in normal mice sy stemically injected with a p75(NGFR)-inhibiting peptide. Control, but not p75(NGFR)-deficient, mice also had fewer cholinergic striatal inte rneurons. Apparently, p75(NGFR) mediates apoptosis of these developing neurons in the absence of TrkA, and modulation of p75(NGFR) can promo te neuronal survival. Cholinergic basal forebrain neurons are involved in learning and memory.