Low concentrations of N-methyl-D-aspartate inhibit the induction of long-term potentiation in rat hippocampal slices.

We have examined the effects of excitatory amino acids on tetanus-induced long-term potentiation (LTP) in the CA1 region of rat hippocampal slices. Agonists acting at N-methyl-D-aspartate (NMDA) receptors, including NMDA, aspartate and glutamate, completely block the development of LTP when administered for 5 min prior to tetanic stimulation. Additionally, and unlike the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV), NMDA blocks LTP when administered for 5 min immediately following the electrical tetanus. The effective concentrations of NMDA are subthreshold for depolarizing CA1 neurons. These results indicate that under certain conditions NMDA receptor activation prevents CA1 LTP.