Differential long-lasting potentiation of the NMDA and non-NMDA synaptic currents induced by metabotropic and NMDA receptor coactivation in cerebellar granule cells

Whole-cell patch-clamp recordings in rat cerebellar slices were used to investigate the effect of metabotropic glutamate receptor activation on mossy fibre-granule cell synaptic transmission. Transient application of 20 microM 1S, 3R-aminocyclopentane-1, 3-dicarboxylic acid simultaneously with low-frequency NMDA receptor activation induced long-lasting non-decremental potentiation of both NMDA and non-NMDA receptor-mediated synaptic transmission. Potentiation could be prevented by application of the metabotropic glutamate receptor antagonist (+)-O-methyl-4-carboxyphenyl-glycine at 500 microM. Characteristically, NMDA potentiation was two to three times as large as non-NMDA current potentiation, occurred only in a slow subcomponent, and was voltage-independent. This result demonstrates a pivotal role of NMDA receptors in the metabotropic potentiation of transmission, which may be important in regulating cerebellar information processing.