Dual mechanism for presynaptic modulation by axonal metabotropic glutamate receptor at the mouse mossy fibre-CA3 synapse.

1. To investigate mechanisms responsible for the presynaptic inhibitory action mediated by the axonal group II metabotropic glutamate receptor (mGluR) at the mossy fibre-CA3 synapse, we used a quantitative fluorescence measurement of presynaptic Ca2+ in mouse hippocampal slices. 2. Bath application of the group II mGluR-specific agonist (2S,1'R,2'R,3'R)-2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV, 1 microM) reversibly suppressed the presynaptic Ca2+ influx (to 55.2 +/- 4.6 % of control, n = 5) as well as field EPSPs recorded simultaneously (to 3.1 +/- 2.0%). Presynaptic fibre volley was not affected by 1 microM DCG-IV. 3. A quantitative analysis of the inhibition of presynaptic Ca2+ influx and field EPSP suggested that DCG-IV suppressed the field EPSP to a greater extent than would be expected if the suppression were solely due to a decrease in the presynaptic Ca2+ influx. 4. DCG-IV at 1 microM suppressed the mean frequency (to 73.8 +/- 3.9% of control, n = 11), but not the mean amplitude (to 97.0 +/- 3.5%), of miniature EPSCs recorded from CA3 neurones using the whole-cell patch-clamp technique. 5. These results suggest that group II mGluR-mediated suppression is due both to a reduction of presynaptic Ca2+ influx and downregulation of the subsequent exocytotic machinery.