AUTONOMOUSLY ACTIVE PROTEIN-KINASE-C IN THE MAINTENANCE PHASE OF N-METHYL-D-ASPARTATE RECEPTOR-INDEPENDENT LONG-TERM POTENTIATION

In area CA1 of the hippocampus, the induction of long term potentiatio n (LTP) requires activation of either N-methyl-D-aspartate receptors ( NMDA receptor-dependent LTP) or voltage-gated Ca2+ channels (NMDA rece ptor-independent LTP). We have investigated biochemical sequelae of NM DA receptor-independent LTP induction. We find that a persistent incre ase in second messenger-independent protein kinase C activity is assoc iated with the maintenance phase of NMDA receptor independent LTP. Thi s increase in protein kinase C activity is prevented by blocking LTP w ith nifedipine, a Ca2+ channel antagonist, or kynurenic acid, a nonsel ective glutamate receptor antagonist. Additionally, we find an increas e in the catalytic fragment of protein kinase C (PKM) in the maintenan ce phase of NMDA receptor-independent LTP, indicating that proteolytic activation of protein kinase C may account for its autonomous activat ion. This increase in the catalytic fragment of protein kinase C is al so prevented by blocking LTP induction. These results are the first to demonstrate that persistent protein kinase C activation is a possible mechanism for the maintenance of NMDA receptor-independent LTP.