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1The aim of the study was to elucidate the mechanisms underlying the depressant effect of the group I/II metabotropic glutamate receptor (mGluR) agonist 1S,3R‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD) on parallel fibre (PF) to Purkinje cell (PC) synaptic transmission. Experiments were performed in rat cerebellar slices using the whole‐cell patch‐clamp technique and fluorometric measurements of presynaptic calcium variation2Analysis of short‐term plasticity, fluctuation of EPSC amplitude and responses of PCs to exogenous glutamate showed that depression caused by 1S,3R‐ACPD is presynaptic.3The effects of 1S,3R‐ACPD were blocked and reproduced by group I mGluR antagonists and agonists, respectively.4These effects remained unchanged in mGluR5 knock‐out mice and disappeared in mGluR1 knock‐out mice.51S,3R‐ACPD increased calcium concentration in PFs. This effect was abolished by AMPA/kainate (but not NMDA) receptor antagonists and mimicked by focally applied agonists of these receptors. Thus, it is not directly due to mGluRs but to presynaptic AMPA/kainate receptors indirectly activated by 1S,3R‐ACPD.6Frequencies of spontaneous and evoked unitary EPSCs recorded in PCs were respectively increased and decreased by mGluR1 agonists. Similar results were obtained when mGluR1s were activated by tetanic stimulation of PFs.7Injecting 30 mmBAPTA into PCs blocked the effects of 1S,3R‐ACPD on unitary EPSCs.8In conclusion, 1S,3R‐ACPD reduces evoked release of glutamate from PFs. This effect is triggered by postsynaptic mGluR1s and thus implies that a retrograde messenger, probably glutamate, opens presynaptic AMPA/kainate receptors and consequently increases spontaneous release of glutamate from PF terminals and decreases evoked synaptic transmission.

RECENT reports have suggested the existence of a causal relationship between impaired regression of multiple climbing fibre innervation and impaired motor coordination in protein kinase Cγ subunit (PKCγ) mutant mice. In the present patch-clamp study, performed in thin cerebellar slices prepared from adult mutant mice deficient in metabotropic glutamate receptors of the mGluR1 subtype, only 15 of Purkinje cells remained multiply innervated by climbing fibres, but motor coordination was largely impaired in these animals. The present results do not preclude the existence of a causal relationship between impairement of regression of multiple innervation during development and improper motor coordination in the adult.