When are class I metabotropic glutamate receptors necessary for long-term potentiation?

The involvement of metabotropic glutamate receptors (mGluRs) in hippocampal long-term potentiation (LTP) is a matter of controversial debate. Using [Ca2+]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)-alpha-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 [Ca2+]i response. As indicated by experiments in which we blocked voltage-dependent calcium channels (VDCCs) and intracellular Ca2+ 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 Ca2+ from ICSs for induction. During strong tetanic stimulation, this Ca2+ source is functionally bypassed by activating VDCCs.