N-METHYL-D-ASPARTATE RECEPTORS

Discovered more than 70 years ago due to advances in electrophysiology and cell culture techniques, N-methyl-D-aspartate (NMDA) receptors remain the target of assiduous basic and clinical research. This interest flows from their intimate engagement with fundamental processes in the mammalian central nervous system and the resulting natural desire to understand how this receptor’s genetically encoded structural properties generate their distinctive functional features and how in turn these unique functional attributes play into the larger opus of physiological and pathological processes. From the overwhelming literature on the subject, the authors briefly outline contemporary understanding of the receptor’s evolutionary origins, molecular diversity, and expression patterns; sketch hypothesized correlations between structural dynamics, signal kinetics, and pathophysiological consequences; and highlight the breadth of processes in which NMDA receptors are implicated, many of which remain poorly understood. Continued developments in cryo-electron microscopy, whole-genome sequencing and editing, imaging, and other emerging technologies will likely confirm some of the current hypotheses and challenge others to produce a more accurate reflection of these receptors’ complex operation and myriad roles in health and disease.