Activation of metabotropic glutamate receptor type 2/3 suppresses transmission at rat hippocampal mossy fibre synapses.

1. The effects of metabotropic glutamate receptor (mGluR) agonists on excitatory transmission at mossy fibre‐CA3 synapses were studied in rat hippocampal slice preparations using both extracellular and whole‐cell clamp recording techniques. 2. Application of a novel and potent mGluR2/mGluR3‐specific agonist (2S,1'R,2'R,3'R)‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV, 0.1 microM) reversibly suppressed field excitatory postsynaptic potentials evoked by mossy fibre stimulation. DCG‐IV at the same concentration did not affect other glutamatergic excitatory transmissions at the commissural/associational input to CA3 or at the Schaffer collateral/commissural input to CA1 regions. 3. This suppressing effect of DCG‐IV on mossy fibre transmission was dose dependent and partly antagonized by a competitive mGluR antagonist (+)‐methyl‐4‐carboxylphenylglycine (1 mM). 4. The field potential changes induced by pressure application of glutamate (0.1 mM) to the stratum lucidum of the CA3 region was unaffected by 0.1 microM DCG‐IV. 5. In whole‐cell clamp experiments, 0.1 microM DCG‐IV suppressed excitatory postsynaptic currents evoked by mossy fibre stimulation without inducing detectable inward current in CA3 neurons, and paired‐pulse facilitation was enhanced by DCG‐IV application. 6. These results suggest that mGluR2/mGluR3 are specifically expressed at mossy fibre synapses in the hippocampal CA3 region, and activation of the receptor suppresses synaptic transmission by an action on a presynaptic site.