Activation of mGluR5 induces spike afterdepolarization and enhanced excitability in medium spiny neurons of the nucleus accumbens by modulating persistent Na+ currents

摘要: The involvement of metabotropic glutamate receptors type 5 (mGluR5) in drug-induced behaviours is well-established but limited information available on their functional roles addiction-relevant brain areas like the nucleus accumbens (NAc). This study demonstrates that pharmacological and synaptic activation mGluR5 increases spike discharge medium spiny neurons (MSNs) NAc. effect was associated with appearance a slow afterdepolarization (ADP) which, voltage-clamp experiments, recorded as slowly inactivating inward current. Pharmacological studies showed ADP elicited by stimulation via G-protein-dependent phospholipase C elevation intracellular Ca2+ levels. Both aftercurrents were significantly inhibited Na+ channel-blocker, tetrodotoxin (TTX). Moreover, selective blockade persistent currents (INaP), achieved NAc slice pre-incubation 20 nm TTX or 10 μm riluzole, reduced amplitude, indicating this current responsible for mGluR5-dependent ADP. also produced significant INaP, prevented mGluR5-induced enhancement discharge. Collectively, these data suggest upregulates INaP MSNs NAc, thereby inducing an results enhanced MSN excitability. Activation will alter firing vivo, could be important mechanism which mediate certain aspects behaviours.