Group I Metabotropic Glutamate Receptors are Required for the Induction of Long-Term Depression at the Medial Perforant Path-Dentate Gyrus Synapse

Group I metabotropic glutamate receptors (mGluRs) modulate synaptic plasticity at most hippocampal synapses. However, the individual contribution of group I mGluRs to the induction of long-term depression (LTD) at synapses between the medial perforant path and dentate granule cells remains unclear. Using extracellular recordings in acute hippocampal slices and pharmacological manipulations of mGluR1 and mGluR5, we investigated their individual contributions to the induction of LTD. Our results demonstrate that although both receptors contribute to synaptic depression, activation of mGluR1 is critical for the induction phase, whereas activation of mGluR5 regulates the magnitude of synaptic depression. Analysis of short-term plasticity revealed that cooperative activation of both receptors maximizes the efficacy of short-term depression during low-frequency stimulation. Additionally, whole-cell recordings showed that activation of group I mGluRs with DHPG modulates voltage-dependent firing rate of mature granule cells. Together, these data reveal functional specialization of mGluR1 and mGluR5 in modulating LTD induction at the medial perforant path-dentate gyrus synapse.