1. The effects of metabotropic glutamate receptor (mGluR) activation on synaptic inhibition were examined using whole‐cell recordings of spontaneous and miniature inhibitory synaptic currents from CA3 pyramidal cells in rat hippocampal slices. 2. The mGluR agonist (1S,3R)trans‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (tACPD) increased spontaneous IPSC (spIPSC) frequency by up to 5‐fold. At doses above 5 microM the increase was transient (15‐45 s) and was followed by a decline to control frequency. In these conditions, elevating external K+ from 2 to 8 mM could still increase spIPSC frequency. 3. Miniature IPSCs (mIPSCs) were recorded in the presence of 1 microM TTX, 5 mM Mg2+ and nominally zero Ca2+. At concentrations above 50 microM, tACPD induced a sustained, reversible reduction in mIPSC frequency by up to 43%. 4. Quisqualate, at doses as low as 50 nM, increased spIPSC frequency, but did not affect mIPSC frequency at concentrations up to 10 microM. 5. The specific mGluR2 and 3 agonist (2S,1'R,2'R,3'R)‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV, 3 microM) reduced mIPSC frequency by 40 +/‐ 4% but did not increase spIPSC frequency. 6. The putative mGluR antagonist L‐2‐amino‐3‐phosphonopropionate (L‐AP3, 1 mM) blocked the effect of tACPD on mIPSC but not spIPSC frequency. The broad‐spectrum antagonist (RS)‐alpha‐methyl‐4‐carboxyphenylglycine (MCPG, 500 microM) blocked both responses. 7. mGluR activation also had dual effects on IPSCs evoked by focal extracellular stimulation. Application of 5 microM tACPD increased the mean amplitude of evoked IPSCs by 112 +/‐ 9%, largely by reducing the proportion of response failures. In contrast, IPSC amplitude was reduced to 44 +/‐ 1% of control values by 3 microM DCG‐IV. 8. These results suggest hippocampal inhibitory cells express two distinct mGluR subtypes. One receptor (possibly mGluR1 or 5) is located on somato‐dendritic membrane and enhances cell excitability. Another (mGluR2 or 3) is present at inhibitory terminals and reduces the probability of GABA release.

Poncer, J. C., Shinozaki, H., & Miles, R. (1995). Dual modulation of synaptic inhibition by distinct metabotropic glutamate receptors in the rat hippocampus. The Journal of Physiology, 485(1), 121–134. Portico.