Metabotropic receptor stimulation coupled to weak tetanus leads to long-term potentiation and a rapid elevation of cytosolic protein kinase C activity

Abstract

We have previously shown that short-term potentiation (STP) inducing weak tetanus induces long-term potentiation (LTP) when it is coupled with 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 LTP involves activation of protein kinase C (PKC). Two minutes but not 30 min after coupling, there was a significant increase in the activator-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-application of γ-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 (<5min) increase in cytosolic PKC activity was also seen after the induction of LTP by stronger tetanic stimulation. No LTP tested in the present study was accompanied by activator-independent, persistent increases in PKC activity. STP induction depends on NMDA receptor activation, and the activation of mGlu receptors results in the production of intracellular second messengers. Our results therefore indicate that these separate components may add and bring about PKC activation and LTP.