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) mediat ed by ionotropic glutamate (iGluR) alpha -amino-3-hydroxy-5-methyl-4-isoxaz olepropionic acid (AMPA) receptors followed by the inhibitory gamma-aminobu tyric acid(A) (GABA(A))-dependent postsynaptic potential. In the presence o f antagonists for iGluRs and for GABA(A) receptors, brief tetanic activatio n evoked a slow metabotropic glutamate receptor (mGluR)-dependent EPSP (mGl uR-EPSP). This mGluR-EPSP was blocked by the selective mGluR1 antagonists L Y367385 and CPCCOEt, but not by the mGluR5 antagonist MPEP. Group II agonis ts affected neither iGluR-EPSP nor mGluR-EPSP. Conversely, L-AP4 and L-SOP, group III mGluR agonists, inhibited both iGluR- and mGluR-EPSPs. The depol arisations evoked by both AMPA and group I agonists were unaffected, indica ting a presynaptic action of group III mGluRs. These data suggest that glut amate released by parallel fibres activates group III mGluR autoreceptors, depressing both iGluR- and mGluR1-mediated EPSPs. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.