Effects of ACPD and AP3 on parallel-fibre-mediated EPSPs of Purkinje cells in cerebellar slices in vitro.

The effects of trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) and of DL-2-amino-3-phosphonopropionic acid (AP3), i.e. selective agonist and antagonist of metabotropic quisqualate receptors respectively, on parallel fibre (PF)-mediated EPSPs of Purkinje cells (PCs) were studied in an in vitro slice preparation. Bath application of 500 microM trans-ACPD in conjunction with PF stimulation at 0.2 or 1 Hz depending on the cell always induced a marked depression of PF-mediated EPSPs, which was fully reversible in most cases after wash-out of this compound. Trans-ACPD also often induced a transient depolarization of PCs which induced calcium spike firing in these cells and which again no longer persisted after wash-out of trans-ACPD. Even in cells which were depolarized by trans-ACPD, the decrease in amplitude of PF-mediated EPSPs started before the appearance of calcium spikes, lasted longer than the transient depolarizing effect of trans-ACPD, and was accompanied by no variation in input resistance of the cells when they were manually clamped at their initial resting potential. Bath application of 600 microM DL-AP3 had no effect on PF-mediated EPSPs or the bioelectrical activities of PCs. Moreover, it did not prevent the effects of trans-ACPD mentioned before. The present results are not consistent with the view that coactivation of ionotropic and metabotropic quisqualate receptors of PCs is sufficient to induce a long-term depression of PF-mediated EPSPs.