Developmental aspects of NMDA receptor function

Glutamate is the major excitatory neurotransmitter in mammalian synapses. It binds to three classes of predominantly postsynaptic ionotropic receptors to activate receptor-associated channels, and a class of metabotropic receptors to activate G-protein mediated transduction pathways. The N-methyl-D-aspartate (NMDA) receptor (NR) is distinctive in being both ligand and voltage-gated, and selectively permeable to Ca2+. As a consequence, NR-mediated alterations in intracellular Ca2+ levels regulate a variety of signaling pathways, ranging from localized, acute effects on receptor and channel activities to long-term effects on nuclear gene transcription. Regulated expression, assembly, and modulation of distinct heteromeric NR complexes comprised of different subunit combinations contributes to this functional diversity. NRs have been implicated in several developmental processes, and evidence supporting their role in migration, survival, and synaptic maturation is discussed.