Selective involvement of mGlu1 receptors in corticostriatal LTD

Although metabotropic glutamate receptors (mGluRs) have been proposed to pl ay a role in corticostriatal long-term depression (LTD), the specific recep tor subtype required for this form of synaptic plasticity has not been char acterized yet. Thus, we utilized a corticostriatal brain slice preparation and intracellular recordings from striatal spiny neurons to address this is sue. We observed that both AIDA (100 muM) and LY 367385 (30 muM), two block ers of mGluR1s, were able to fully prevent the induction of this form of sy naptic plasticity, whereas MPEP (30 muM), a selective antagonist of the mGl uR5 subtype, did not significantly affect the amplitude and time-course of corticostriatal LTD. Both AIDA and LY 367385 were ineffective on LTD when a pplied after its induction. The critical role of mGluR1s in the formation o f corticostriatal LTD was confirmed in experiments performed on mice lackin g mGluR1s. In these mice, in fact, a significant reduction of the LTD ampli tude was observed in comparison to the normal LTD measured in their wild-ty pe counterparts. We found that neither acute pharmacological blockade of mG luR1s nor the genetic disruption of these receptors affected the presynapti c modulation of corticostriatal excitatory postsynapic potentials (EPSPs) e xerted by DCG-IV and L-SOP, selective agonists of group II and III mGluRs, respectively. Our data show that the induction of corticostriatal LTD requires the activa tion of mGluR1 but not mGluR5. mGluR1-mediated control of this form of syna ptic plasticity may play a role in the modulatory effect exerted by mGluRs in the basal ganglia-related motor activity. (C) 2001 Elsevier Science Ltd. All rights reserved.