INHIBITION OF A SLOW SYNAPTIC RESPONSE BY A METABOTROPIC GLUTAMATE-RECEPTOR ANTAGONIST IN HIPPOCAMPAL CA3 PYRAMIDAL CELLS

The effects of a novel antagonist of metabotropic glutamate receptors were investigated in CA3 pyramidal cells in hippocampal slice cultures of the rat. Earlier experiments showed that selective activation of m etabotropic glutamate receptors with low concentrations of an agonist, 1S, 3R-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD), induced an inward current associated with a decrease in membrane conductance and inhibition of the slow calcium-dependent potassium current. These resp onses were strongly and reversibly reduced by the antagonist, (RS)-alp ha-methyl-4-carboxyphenylglycine (MCPG, 0.5-1 mm). In the presence of antagonists of ionotropic glutamate receptors, stimulation of the affe rent mossy fibres evoked postsynaptic responses in CA3 pyramidal cells which paralleled those observed with exogenously applied metabotropic glutamate receptor agonists, i.e. a slow inward current and a reducti on of calcium-dependent potassium current. Both responses were greatly reduced by bath-applied MCPG (1 mm). These results show that MCPG act s as an effective antagonist at metabotropic glutamate receptors coupl ed to potassium conductances in the hippocampus. Furthermore, they con firm that glutamate release from presynaptic terminals can modulate po stsynaptic properties by activation of metabotropic glutamate receptor s.