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

Abstract

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.Bath application of the group II mGluR-specific agonist (2S,1′R,2′R,3′R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 1 μM) 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 μM DCG-IV.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.DCG-IV at 1 μM 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.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.