GluN3 subunit-containing NMDA receptors: not just one-trick ponies

The two GluN3 subunits were the last NMDA receptor subunits to be cloned some 15 years ago. Strikingly, despite the steadily growing interest in their function, their physiological role remains elusive. The original billing as dominant-negative modulators of classical NMDA receptors composed of GluN1 and GluN2 subunits has given way to proposals of much more complex functions, including roles in synaptogenesis and synaptic plasticity. In addition, GluN3 subunits in the absence of GluN2 surprisingly assemble with GluN1 into excitatory glycine receptors. This review provides an overview of the unique spatial and temporal expression patterns of the GluN3 subunits, discusses proposed functions and physiological roles for receptors comprising these subunits, and briefly summarizes their putative involvement in several neural diseases.