POTENTIATION OF CAMP RESPONSES BY METABOTROPIC GLUTAMATE RECEPTORS DEPRESSES EXCITATORY SYNAPTIC TRANSMISSION BY A KINASE-INDEPENDENT MECHANISM

Coactivation of metabotropic glutamate receptors (mGluRs) and beta-adr energic receptors causes a synergistic increase in cAMP formation in t he rat hippocampus. Increases in cAMP are known to have many actions i n the hippocampus via activation of cAMP-dependent protein kinase. We now report that coactivation of mGluRs and beta-adrenergic receptors i nduces an acute depression of EPSCs at the Schaffer collateral-CA1 syn apse. Interestingly, this depression of EPSCs is dependent upon increa ses in cAMP levels but independent of protein kinase activity. A serie s of studies suggests that cAMP-mediated depression of EPSCs is depend ent on metabolism of cAMP and release of adenosine or 5'-AMP into the extracellular space with resultant activation of presynaptic adenosine receptors. These studies suggest that cAMP can have local hormone-lik e effects in the hippocampal formation which are independent of cAMP-d ependent protein kinase.