Neurotrophic effects of NMDA receptor activation on developing cerebellar granule cells

Glutamate acting on N-methyl-D-aspartate (NMDA) receptors controls a variety of aspects of neuronal plasticity in the adult and developing brain. This review summarizes its effects on developing cerebellar granule cells. The glutamatergic mossy fibre input to cerebellar granule cells exerts a neurotrophic effect on these cells during development. The investigation of potential neurotrophic agents can be carried out using enriched granule cell cultures. Considerable evidence now indicates that glutamate acting on N-methyl-D-aspartate receptors is an important neurotrophic factor that regulates granule cell development. In culture, neurite growth, differentiation and cell survival are all stimulated by N-methyl-D-aspartate receptor activation. The intracellular pathways involved following Ca2+ entry through the N-methyl-D-aspartate receptor channel are beginning to be elucidated. The cerebellar granule cell culture system may provide an ideal model to investigate the molecular mechanisms involved in long term N-methyl-D-aspartate receptor-mediated changes in neuronal function.