A role for protein kinase C in a form of metaplasticity that regulates theinduction of long-term potentiation at CA1 synapses of the adult rat hippocampus

The possibility that protein kinase C (PKC) is involved in the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP ) at CA1 synapses in the hippocampus has been the subject of considerable i nvestigation. However, many of the conclusions have been drawn from the use of relatively nonspecific PKC inhibitors. In the present study we have exa mined the role of PKC in tetanus-induced LTP of AMPA receptor-mediated syna ptic transmission in hippocampal slices obtained from adult rats. In partic ular, we have investigated the possible role of PKC in a molecular switch p rocess that is triggered by the synaptic activation of metabotropic glutama te receptors and regulates the induction of LTP. We find that the three PKC inhibitors examined, chelerythrine, Ro-31-8220 and Go 6983, all block the setting of the molecular switch at concentrations consistent with inhibitio n of PKC. In contrast, these inhibitors are without affect on the induction of LTP, even when applied in very much higher concentrations. A PKA inhibi tor, Rp-cAMPS, had no effect on either process. We suggest that neither PKC nor PKA is required to induce LTP at this synapse. However, PKC is involve d in the regulation of LTP induction, via the molecular switch process.