Regulation of Vulnerability to NMDA Excitotoxicity During Postnatal Maturation

Hippocampal and cortical vulnerability to injury following activation of N-methyl-d-aspartate (NMDA) receptors increases markedly during development from embryonic life to the adult. The mechanisms underlying this increased vulnerability are multiple, and include developmental regulation of NMDA receptor subunit expression, localization of NMDA to synapses or extrasynaptic locations, and intracellular metabolism of NMDA-induced increases in cytosolic calcium concentrations, particularly by mitochondria. The role of nitric oxide is highlighted, especially with new data demonstrating a role for mitochondrial nitric oxide syn-thase (NOS) as a primary mediator of the decreased vulnerability of immature neurons to excitotoxicity.