Cell-type specificity of mGluR activation in striatal neuronal subtypes

The effects of metabotropic glutamate receptor (mGluR) activation were stud ied in medium spiny neurons and large aspiny (LA) interneurons by means of electrophysiological and optical recordings. DCG-IV and L-SOP, agonists for group II and III mGluRs, respectively, produced a presynaptic inhibitory e ffect on corticostriatal glutamatergic excitatory postsynaptic potentials ( EPSPs) in both spiny and LA cells. Activation of group I mGluRs by the sele ctive agonist 3,5-DHPG produced no effect on membrane properties and glutam atergic transmission in spiny neurons, whereas it did cause a membrane depo larization in LA interneurons coupled to increased input resistance. In com bined optical and electrophysiological experiments, in spiny neurons 3,5-DH PG enhanced membrane depolarization and intracellular calcium (Ca2+) levels induced by NMDA applications, but not in LA interneurons. These data sugge st the existence of a positive interaction between NMDA and group I mGlu re ceptors only in medium spiny cells which might, at least partially, account for the differential vulnerability to excitotoxic damage observed in stria tal neuronal subtypes.