METABOTROPIC RECEPTOR STIMULATION COUPLED TO WEAK TETANUS LEADS TO LONG-TERM POTENTIATION AND A RAPID ELEVATION OF CYTOSOLIC PROTEIN-KINASE-C ACTIVITY

We have previously shown that short-term potentiation (STP) inducing w eak tetanus induces long-term potentiation (LTP) when it is coupled wi th activation of metabotropic glutamate (mGlu) receptors by trans-(+/- )-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD) in rat CA1 slices 2,55. In the present study, we examined if this conversion of STP to L TP involves activation of protein kinase C (PKC). Two minutes but not 30 min after coupling, there was a significant increase in the activat or-dependent PKC activity in the cytosolic fraction. STP induction or t-ACPD application did not change PKC activity. There was no activity increase in the membrane fraction. STP was also induced by a co-applic ation of mma-amino-3-hydroxy-5-methyllisoxazole-4-propionic acid (AMPA ) and N-methyl-D-aspartic acid (NMDA). Coupling this STP with t-ACPD, however, did not result in an LTP or PKC activity increase, indicating a requirement for synaptic activity. A rapid and transient (< 5 min) increase in cytosolic PKC activity was also seen after the induction o f LTP by stronger tetanic stimulation. No LTP tested in the present st udy was accompanied by activator-independent, persistent increases in PKC activity. STP induction depends on NMDA receptor activation, and t he activation of mGlu receptors results in the production of intracell ular second messengers. Our results therefore indicate that these sepa rate components may add and bring about PKC activation and LTP.