N-methyl-D-aspartate receptor activation is required for the induction of both early and late phases of long-term potentiation in rat hippocampal slices.

The possible involvement of N-methyl-D-aspartate (NMDA) receptors in mechanisms enabling the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of the specific NMDA receptor antagonists (-)-2-amino-7-phosphonoheptanoic acid (D-APH) and 2-amino-5-phosphonovaleric acid (DL-APV) as well as of the inactive isomer L-APH was tested on orthodromic population excitatory postsynaptic potential (EPSP) and population spike (PS) responses recorded extracellularly from CA1 pyramidal cells. If the active D-isomer of APH (10 microM) or DL-APV (50 microM), but not if L-APH was present during tetanization, both EPSP and spike potentiation were markedly reduced or even blocked for the whole recording period (8 h after tetanization). It is concluded that the NMDA receptor component expressed during tetanization is a necessary step not only for initiation but also for subsequent mechanisms enabling late phases of synaptic LTP. Some remaining potentiation of the population spike may be related to a second, NMDA-independent mechanism.