PRESYNAPTIC DEPRESSION OF INHIBITORY POSTSYNAPTIC POTENTIALS BY METABOTROPIC GLUTAMATE RECEPTORS IN RAT HIPPOCAMPAL CA1 PYRAMIDAL CELLS

The effects of the metabotropic glutamate (mGlu) receptor agonists (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or 1S,3R-ACPD on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic responses have been investigated in vitro in CA1 pyramidal cells of rat hippocampal slices. Bath application of both agonists depolarized the resting membrane potential and increased membrane resistance. Simultaneously, the afterhyperpolarization induced by a burst of spikes as well as spike accomodation were blocked. Stimulation of the stratum radiatum induced in CA1 pyramidal cells an early excitatory postsynaptic potential (EPSP) followed by a fast GABA(A) and a slow GABA(B)-mediated inhibitory postsynaptic potentials (IPSPs). All synaptic responses were dose dependently depressed by mGlu receptor agonists. At low concentration, (+/-)-trans-ACPD (10-100 mu M) and 1S,3R-ACPD (10 mu M) consistently reduced the EPSP, slightly depressed the fast IPSP but greatly decreased the slow IPSP. Increasing the concentration of mClu receptor agonists to 200 mu M and 50 mu M, respectively further depressed the EPSP and dramatically reduced the amplitude of both IPSPs. In the presence of the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M) and D-(-)-2-amino-5-phosphonovaleric acid (30 mu M), monosynaptically evoked IPSPs were still depressed by mGlu receptor agonists. In the same conditions, the discharge frequency of spontaneous IPSPs which reflect the activity of GABAergic interneurons was enhanced by low doses of mGlu receptor agonists but depressed with higher concentrations. On the other hand, the postsynaptic hyperpolarization and decrease in membrane resistance induced by the GABA(B) receptor agonist baclofen applied in the bath or by microiontophoresis were not affected by mGlu receptor agonists. These results indicate that the GABA-mediated IPSPs of CA1 hippocampal pyramidal cells are depressed by mGlu receptors located on presynaptic GABAergic terminals. Such heteroreceptors by inhibiting the release of GABA may account for the facilitatory effect of mGlu receptors in the mechanisms of neuronal plasticity.