NMDA receptors require binding of two ligands: agonist, glutamate and co-agonist, glycine or D-serine. The extracellular ligand binding domain in GluN1 (GRIN1, NR1) subunits binds co-agonist glycine or D-serine and the extracellular ligand binding domain in GluN2 (GRIN2, NR2) binds glutamate. In total, two molecules of glycine or D-serine (one for each of the two GluN1 subunits) and two molecules of glutamate (one for each of the two GluN2 subunits) are bound to activate one NMDA receptor (Kleckner and Dingledine 1988, Benveniste and Mayer 1991, Furukawa et al. 2005).