Modulatory action of metabotropic glutamate receptor (mGluR) 5 on mGluR1 function in striatal cholinergic interneurons

Within basal ganglia, group I metabotropic glutamate receptor subtypes (mGluR1 and 5) frequently co-localize in the same neuron. However, little is known about how these receptors functionally interact. We addressed this issue by means of electrophysiological recordings of striatal cholinergic interneurons, a neuronal subtype that co-express both group I mGluRs. The group I non-selective agonist 3,5-DHPG induced a membrane depolarization/inward current that was prevented by co-application of LY 367385, a selective mGluR1 antagonist, and SIB 1757 or MPEP, blockers of mGluR5 subtype. The reversal potential for the response to 3,5-DHPG was close to the equilibrium potential for potassium channels. Repeated bath or focal applications of 3,5-DHPG induced a progressive decline in the amplitude of the membrane depolarization, suggesting that group I mGluRs undergo receptor desensitization. Interestingly, in the presence of the mGluR5 blocker, SIB 1757, this event was not observed, whereas it occurred in LY 367385. PKC blockers chelerythrine and calphostin C mimicked the inhibitory effect of SIB 1757. In a subset of interneurons, in MPEP or SIB 1757, 3,5-DHPG induced a 0.5-1 Hz oscillatory response, that was prevented by L-type Ca2+ channel blockers, and by the tyrosine kinase inhibitors genistein and lavendustin. Together, these data suggest that mGluR5 modulates mGluR1 activity to shape cell excitability. (c) 2005 Elsevier Ltd. All rights reserved.