METABOTROPIC GLUTAMATE RECEPTORS MODULATE N-METHYL-D-ASPARTATE RECEPTOR FUNCTION IN NEOSTRIATAL NEURONS

The functional roles played by metabotropic glutamate receptors in the neostriatum is just beginning to be examined. One possibility, raised by previous studies, is that metabotropic glutamate receptors act to modulate responses mediated by ionotropic glutamate receptors. In the present study, we examined this possibility in a neostriatal brain sli ce preparation using intracellular recording and iontophoretic techniq ues. We found that the iontophoretic application of the metabotropic g lutamate receptor agonist 1-amino-cyclopentane-1,3-dicarboxylic acid m arkedly attenuated both the amplitude and duration of excitatory respo nses induced by the iontophoretic application of N-methyl-D-aspartate. These inhibitory effects were stereo-selective and relatively long-la sting. The metabotropic glutamate receptor antagonist 2-amino-3-phosph onopropionic acid applied either iontophoretically or in the bath prev ented the inhibitory effects of 1-amino-cyclopentane-1,3-dicarboxylic acid. The inhibitory action of 1-amino-cyclopentane-1,3-dicarboxylic a cid was specific to N-methyl-D-aspartate, as 1-amino-cyclopentane-1,3- dicarboxylic acid had no consistent action on the responses evoked by the iontophoretic application of glutamate, amino-3-hydroxy-5-methyl-4 -isoazolepropionic acid or quisqualate. Bath application of 1-amino-cy clopentane-1,3-dicarboxylic acid inhibited the evoked depolarizing pos tsynaptic potentials recorded in neostriatal cells. Thus, activation o f metabotropic glutamate receptors may play an important role in modul ating N-methyl-D-aspartate receptor function in neostriatal neurons.