AbstractIn patch‐clamped Purkinje cells (PCs), bath application of the ionotropic glutamate receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) prevents induction of long‐term depression (LTD) of parallel fibre (PF)‐mediated EPSPs by a pairing protocol between Ca2+spike firing and PF stimulation whereas bath application of (RS)‐α‐methyl‐4‐carboxyphenylglycine (MCPG), a metabotropic glutamate (mGLU) receptor antagonist, does not. On the other hand, LTD can be also induced by pairing direct depolarization of PCs with activation of mGLU receptors by 1 S,3R‐aminocyclopentyl‐dicarboxylate (1S, 3R‐ACPD), even in the presence of CNQX. In this case, LTD induction is not consistently blocked by bath application of the nitric oxide synthase inhibitor,NG‐methyl‐l‐arginine (l‐NMMA), whereas it is strongly blocked when the protein kinase C inhibitor peptide 19‐36 is dialysed into PCs. These results are at variance with LTD induced by a pairing protocol between Ca2+spikes and PF‐mediated EPSPs which depends to the same extent on both cascades. Finally, thapsigargin, which depletes most intracellular Ca2+pools, does not block induction of LTD by a pairing protocol between Ca2+spikes and PF‐mediated EPSPs whereas it prevents the induction of LTD