In the Newborn Hippocampus, Neurotrophin-Dependent Survival Requires Spontaneous Activity and Integrin Signaling

Abstract

The nervous system develops through a program that first produces neurons in excess and then eliminates as many as half in a specific period of early postnatal life. Neurotrophins are widely thought to regulate neuronal survival, but this role has not been clearly defined in the CNS. Here we show that neurotrophins promote survival of young neurons by promoting spontaneous activity. Survival of hippocampal neurons in neonatal rat requires spontaneous activity that depends on the excitatory action of GABA. Neurotrophins facilitate recruitment of cultured neurons into active networks, and it is this activity, combined with integrin receptor signaling, that controls neuronal survival. In vivo, neurotrophins require integrin signaling to control neuron number. These data are the first to link the early excitatory action of GABA to the developmental death period and to assign an essential role for activity in neurotrophin-mediated survival that establishes appropriate networks.