HETEROGENEITY OF METABOTROPIC GLUTAMATE RECEPTORS IN THE STRIATUM - ELECTROPHYSIOLOGICAL EVIDENCE

In order to investigate the functional role of metabotropic glutamate receptors (mGluRs) in the striatum we performed extracellular and intr acellular recordings from a corticostriatal brain slice preparation. T he effects of L-2-amino-3-phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long-term synaptic depression (LTD) a nd on presynaptic inhibition of excitatory postsynaptic potentials (EP SPs) induced by different agonists of mGluRs. L-AP3 produced a dose-de pendent (3 - 30 muM) reduction of the LTD evoked in the striatum by th e tetanic stimulation of the corticostriatal pathway. In contrast to t his action, L-AP3 (10 - 100 muM) did not significantly affect the pres ynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic ac id (t-ACPD), an agonist of mGluRs, on corticostriatal transmission. Hi gher concentrations Of L-AP3 (0.3 - 1 mM) reduced by themselves the EP SP amplitude. The inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a glutamate autoreceptor agoni st. In some neurons, these inhibitory actions were coupled with membra ne depolarizations. The depression of synaptic transmission caused by t-ACPD. 1S,3R-ACPD and L-AP4 was not altered following the induction o f LTD. Chronic lithium treatment of the animals (60 - 120 mg/kg i.p. f or 1 0 days) blocked striatal LTD but not presynaptic inhibition media ted by mGluR agonists. The present findings show that the mechanisms u nderlying LTD and the presynaptic inhibition induced by different agon ists of mGluRs exhibit functional and pharmacological differences. The se data suggest heterogeneity of mGluRs in the striatum.