PRESYNAPTIC INHIBITION OF EXCITATORY SYNAPTIC TRANSMISSION BY MUSCARINIC AND METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION IN THE HIPPOCAMPUS - ARE CA2+ CHANNELS INVOLVED

Activation of either muscarinic cholinergic or metabotropic glutamater gic presynaptic receptors inhibits evoked excitatory synaptic response s in the hippocampus. We have investigated two possible mechanisms und erlying these actions using whole-cell recording from CA3 pyramidal-ce lls in hippocampal slice cultures. Application of either methacholine (MCh, 10 mu M) or trans-aminocyclopentane-1,3-dicarboxylic acid (t-ACP D, 10 mu M) was found to reduce the frequency of miniature excitatory postsynaptic currents (mEPSCs) by roughly 50%, without changing their mean amplitude. The voltage-dependent Ca2+ channel blocker Cd2+ (100 m u M), in contrast, had no effect on the mEPSC frequency. When the extr acellular [K+] was increased from 2.7 to 16 mM, the mEPSC frequency in creased from 1.7 to 4.9 Hz. This increase could be completely reversed by applying Cd2+, indicating that it was triggered by voltage-depende nt Ca2+ influx. MCh and t-ACPD each decreased the mEPSC frequency by r oughly 50% under these conditions. Because the agonists were equally e ffective in inhibiting spontaneous release whether voltage-dependent c hannels were activated or not, we conclude that presynaptic cholinergi c and glutamatergic inhibition is not mediated by inhibition of presyn aptic Ca2+ channels, but rather by a direct interference in the neurot ransmitter release process at some point subsequent to Ca2+ influx.