The phenomena of LTP and LTD are extensively studied in synapses located in the hippocampus [51–54]. Whereas LTP was originally induced in the hippocampus by stimulation of axons of the perforant path and potentiation of the postsynaptic potentials in the dentate gyrus [55], the potentiation was found to be input-specific. That is, stimulation of the medial perforant path did not potentiate the lateral perforant path and vice versa. Later, Collingridge et al. made the key observation that the selective NMDAR antagonist AP-5 blocks the induction of LTP in the Schaffer collateral-commissural pathway of the hippocampus [56], indicating a direct role for NMDARs in mediating hippocampal LTP. At the same time, Lynch et al. illustrated that intracellular injection of the calcium chelator N,N,N’,N’-tetraacetic acid (EGTA) into pyramidal cells of the CA1 region of the hippocampus blocked the induction of LTP suggesting that NMDARs are the source of calcium that supports this form of LTP [16]. Additional mechanistic studies have demonstrated that both GluN2A and GluN2B subunits of NMDARs play a significant role in induction of hippocampal LTP [57–59]. More notable is
