Presynaptic modulation by group III metabotropic glutamate receptors (mGluRs) of the excitatory postsynaptic potential mediated by mGluR1 in rat cerebellar Purkinje cells.

Purkinje neurons were recorded from rat cerebellar slices. Parallel fibres stimulation elicited a fast excitatory postsynaptic potential (EPSP) mediated by ionotropic glutamate (iGluR) -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors followed by the inhibitory gamma-aminobutyric acidA (GABAA)-dependent postsynaptic potential. In the presence of antagonists for iGluRs and for GABAA receptors, brief tetanic activation evoked a slow metabotropic glutamate receptor (mGluR)-dependent EPSP (mGluR-EPSP). This mGluR-EPSP was blocked by the selective mGluR1 antagonists LY367385 and CPCCOEt, but not by the mGluR5 antagonist MPEP. Group II agonists affected neither iGluR-EPSP nor mGluR-EPSP. Conversely, L-AP4 and L-SOP, group III mGluR agonists, inhibited both iGluR- and mGluR-EPSPs. The depolarisations evoked by both AMPA and group I agonists were unaffected, indicating a presynaptic action of group III mGluRs. These data suggest that glutamate released by parallel fibres activates group III mGluR autoreceptors, depressing both iGluR- and mGluR1-mediated EPSPs.