Cooperativity between activation of metabotropic glutamate receptors and NMDA receptors in the induction of LTP in hippocampal CA1 neurons.

In CA1 neurons of guinea pig hippocampal slices, long-term potentiation (LTP) was induced by 10 min application of 10 microM aminocyclopentane-1S, 3R-dicarboxylic acid (ACPD), the metabotropic glutamate receptor (mGluR) agonist, in the presence of test synaptic inputs (once every 20 s). In contrast, long-term depression (LTD) was induced by application of 10 microM ACPD in the absence of test inputs. When 10 microM ACPD was applied in the presence of test inputs, co-application of the N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate resulted in LTD induction when used at 50 microM. In ACPD-induced LTP, the delivery of test synaptic inputs to CA1 neurons could be replaced by co-application of NMDA (100 nM) during ACPD perfusion. These results suggest that, in CA1 neurons, a co-operative effect involving the activation of both mGluRs and NMDA receptors is required to trigger the process involved in ACPD-induced LTP. In addition, ACPD-induced LTD was blocked by co-application of an inositol 1,4,5-trisphosphate (IP3) receptor inhibitor, 2-aminotheoxydiphenyl borate (10 microM), which had no effect on ACPD-induced LTP. The results of the present study, therefore, indicate that ACPD-induced LTP involves NMDA receptors, but not IP3 receptors, whereas the converse applies to ACPD-induced LTD.