[Dynamic regulation of the NMDA receptor channel subunits in the central nervous system and their involvement in...

The N-methyl-D-aspartate (NMDA) receptor channel plays a key role in activity-dependent synaptic plasticity in the central nervous system. The channel is also involved in neural development, including experience-dependent changes in neuro-behaviors and synaptic refinement. Molecular biological studies have revealed its heteromeric configuration, consisting of the epsilon (NR2) and zeta 1 (NR1) subunits. The zeta 1 subunit is an essential subunit component to form functional NMDA receptor channels, while four members of the epsilon subunits potentiate the channel activity and modulate the functional properties. In situ hybridization has elucidated distinct spatial and temporal expressions of each epsilon subunit, in contrast to ubiquitous and stable expression of the zeta 1 subunit. Furthermore, recent analyses with mutant mice defective in respective NMDA receptor subunits are providing direct evidence for their disparate physiological roles in synaptic plasticity and development. This review summarizes the recent progress from the molecular-anatomical point of view.