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 r at hippocampal slices. Bath application of both agonists depolarized t he resting membrane potential and increased membrane resistance. Simul taneously, the afterhyperpolarization induced by a burst of spikes as well as spike accomodation were blocked. Stimulation of the stratum ra diatum induced in CA1 pyramidal cells an early excitatory postsynaptic potential (EPSP) followed by a fast GABA(A) and a slow GABA(B)-mediat ed inhibitory postsynaptic potentials (IPSPs). All synaptic responses were dose dependently depressed by mGlu receptor agonists. At low conc entration, (+/-)-trans-ACPD (10-100 mu M) and 1S,3R-ACPD (10 mu M) con sistently reduced the EPSP, slightly depressed the fast IPSP but great ly decreased the slow IPSP. Increasing the concentration of mClu recep tor agonists to 200 mu M and 50 mu M, respectively further depressed t he EPSP and dramatically reduced the amplitude of both IPSPs. In the p resence of the glutamate receptor antagonists 6-cyano-7-nitroquinoxali ne-2,3-dione (10 mu M) and D-(-)-2-amino-5-phosphonovaleric acid (30 m u M), monosynaptically evoked IPSPs were still depressed by mGlu recep tor agonists. In the same conditions, the discharge frequency of spont aneous IPSPs which reflect the activity of GABAergic interneurons was enhanced by low doses of mGlu receptor agonists but depressed with hig her concentrations. On the other hand, the postsynaptic hyperpolarizat ion and decrease in membrane resistance induced by the GABA(B) recepto r agonist baclofen applied in the bath or by microiontophoresis were n ot 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 het eroreceptors by inhibiting the release of GABA may account for the fac ilitatory effect of mGlu receptors in the mechanisms of neuronal plast icity.