The involvement of metabotropic glutamate receptors (mGluRs) in hippocampal long-term potentiation (LTP) is a matter of controversial debate. Using [Ca 2ϩ ] i measurements by confocal laser scanning microscopy and field recordings of EPSPs (fEPSPs) in the hippocampal CA1-region, we found that the efficacy of the broad-spectrum mGluR-antagonist (S)-␣-methyl-4-carboxyphenylglycine (MCPG) and of (S)-4-carboxy-phenylglycine (4-CPG), a selective antagonist at class I mGluRs, in LTP is contingent on the tetanization strength and the resulting [Ca 2ϩ ] i response. As indicated by experiments in which we blocked voltage-dependent calcium channels (VDCCs) and intracellular Ca 2ϩ stores (ICSs), the functional significance of class I mGluRs in LTP is confined to certain types of potentiation, which are induced by weak tetanization protocols and require the release of Ca 2ϩ from ICSs for induction. During strong tetanic stimulation, this Ca 2ϩ source is functionally bypassed by activating VDCCs.

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