Metabotropic glutamate receptors mediate a post-tetanic excitation of guinea-pig hippocampal inhibitory neurones.

1. Inhibitory cell activity and inhibitory postsynaptic potentials impinging spontaneously on pyramidal cells were recorded in the CA3 region of hippocampal slices from guinea-pig. We compared the effects on synaptic inhibition, of tetanic stimuli in the presence of antagonists of ionotropic excitatory amino acid receptors, and of application of agonists of metabotropic glutamate receptors. 2. Tetanic stimulation of afferent fibres caused an increase, of duration 0.5-2.5 min, in the frequency of spontaneous Cl(-)-mediated IPSPs. Inhibitory cell firing increased due to a depolarization and a reduction of after-hyperpolarizing potentials. 3. Tetanic stimulation induced, in some experiments, rhythmic bursts of IPSPs and transformed the firing pattern of some inhibitory cells from a discharge of single action potentials to rhythmic bursts of three to five action potentials. 4. Application of the metabotropic glutamate receptor agonist, trans-1-amino-cyclopentane-1,3-dicarboxylic acid (tACPD), at concentrations from 3-10 microM increased the frequency of spontaneous IPSPs. In some slices tACPD caused IPSPs to occur rhythmically. IPSP frequency did not continue to increase with concentrations of tACPD above 20 microM. 5. tACPD depolarized inhibitory cells and reduced after-hyperpolarizing potentials. High concentrations (50-100 microM) of tACPD excited inhibitory cells to potentials at which they no longer discharged fast action potentials. 6. Both tetanic stimulation and tACPD led to the appearance in pyramidal cell pairs of simultaneous IPSPs which were not previously observed, suggesting that the same group of inhibitory cells was excited in both cases. 7. Low concentrations of tACPD (3-10 microM) enhanced IPSP responses to tetanic stimuli, while the effects of tetanic stimuli were occluded in the presence of high concentrations (20-30 microM) of tACPD. 8. We suggest that activation of metabotropic glutamate receptors during tetanic stimulation leads to a post-tetanic excitation of inhibitory cells that mediate Cl(-)-dependent IPSPs.