Abstract

The neurotrophins are a family of secreted proteins that potently regulate diverse neuronal responses. The neurotrophin nerve growth factor (NGF) and its receptors TrkA and p75 are well characterized to control survival, differentiation and function of many neurons in the peripheral nervous system. The function of NGF/TrkA signaling in the central nervous system (CNS) is less well analyzed. In the CNS all cholinergic neurons of the basal forebrain are NGF-responsive. In this work a genetic mouse model is presented in which NGF/TrkA signaling is specifically deleted from the cholinergic neurons of the basal forebrain. This model demonstrates that NGF/TrkA signaling is essential for the cholinergic differentiation of many neurons in the basal forebrain. In addition, it is shown that the deletion of TrkA signaling modulates the processing of the amyloid precursor protein APP in the basal forebrain.