A glia-derived signal regulating neuronal differentiation

Astrocytes are present in large numbers in the nervous system, are associat ed with synapses, and propagate ionic signals. Astrocytes influence neurona l physiology by responding to and releasing neurotransmitters, but the mech anisms that establish the close interaction between these cells are not def ined. Here we use hippocampal neurons in culture to demonstrate that vasoac tive intestinal polypeptide (VIP) promotes neuronal differentiation through activity-dependent neurotrophic factor (ADNF), a protein secreted by VIP-s timulated astroglia. ADNF is produced by glial cells and acts directly on n eurons to promote glutamate responses and morphological development. ADNF c auses secretion of neurotrophin 3 (NT-3), and both proteins regulate NMDA r eceptor subunit 2A (NR2A) and NR2B. These data suggest that the VIP-ADNF-NT -3 neuronal-glial pathway regulates glutamate responses from an early stage in the synaptic development of excitatory neurons and may also contribute to the known effects of VIP on learning and behavior in the adult nervous s ystem.