The continually evolving role of NMDA receptors in neurobiology and disease

40 years ago, Jeff Watkins and Richard (Dick) Evans (Watkins and Evans, 1981) published their review on excitatory amino acids. The review, combined with the tools that they and their colleagues developed, significantly changed the field of neurobiology. This Special Issue focused on NMDA receptors is one of six that commemorate this anniversary. The broadest impact of the review, and the work of this group (Collingridge and Abraham, 2022; Evans and Watkins, 2021; Watkins, 2000), was to establish the three receptor scheme for the excitatory, l-glutamate-gated ion channels named for their selective agonists: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-d-aspartate (NMDA) (Monaghan et al., 1989; Watkins et al., 1990; Watkins, 2000; Hansen et al., 2021; Lodge, 2009; Watkins and Jane, 2006). The contribution of the Evans and Watkins team was perhaps greatest to the study of NMDA receptors - it was essential. We describe here this fundamental contribution and provide an update on NMDARs as the understanding of their function continues to grow more complex.