NMDA receptors are activated in a two-step mechanism, first by ligand binding and then by removal of the voltage dependent Mg2+ block. At resting membrane potential, NMDA receptors can bind the agonist (glutamate) and the co-agonist (glycine), but cannot be activated by ligand alone due to the presence of Mg2+ ion in the pore of the channel. Then, the membrane is depolarized, through the influx of Na+ through other membrane resident channels, which triggers the removal of Mg2+ from the NMDA receptor pore. Once Mg2+ is expelled, ligand-bound NMDA receptors become active (Wollmuth et al. 1998, Clarke et al. 2013).