Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors

A series of omega-phosphono-alpha-carboxylic acids were tested as antagonists of excitatory amino acid depolarizations and long-term potentiation (LTP) in region CA1 of rat hippocampal slices. The 5- and 7-phosphono compounds (+/- AP5 and +/- AP7) blocked N-methyl-D-aspartate (NMDA) depolarizations and prevented the induction of LTP of the synaptic field potential and population spike components of the Schaffer collateral response. +/- AP5 and +/- AP7 did not reduce kainate or quisqualate depolarizations and did not affect unpotentiated synaptic response amplitude. +/- AP4, +/- AP6 and +/- AP8 did not block amino acid excitant responses or LTP. These results demonstrate that NMDA receptors present in hippocampal region CA1 are not necessary for normal synaptic transmission, but are involved in the initiation of long-term synaptic plasticity.