Activation of the glycine site associated with the NMDA receptor is required for induction of LTP in neonatal hippocampus.

The role played by the glycine site associated with the NMDA receptor in inducing long-term potentiation (LTP) in neonatal hippocampus was examined. An antagonist of the glycine site, 7-chlorokynurenic acid (Cl-Kyn), completely blocked both the short-term and the long-term potentiation associated with theta burst stimulation (TBS) linked to NMDA receptor activation in slices from hippocampus at postnatal days 10-16; this effect was reversed by the glycine agonist, D-serine. Analysis of the TBS-evoked responses showed: (1) a developmental alteration in the burst response morphology that may be related to maturation of GABA-mediated inhibition; and (2) that, unlike 2-amino-5-phosphonovalerate (AP5), Cl-Kyn did not reduce any portion of the burst response. These results suggest that stimulation of the glycine site coupled to the NMDA receptor complex is necessary to induce LTP in neonatal tissue and that two NMDA receptor types may be present in the hippocampus.