Acta Physiologica 2009; Volume 197, Supplement 672
The 60th National Congress of the Italian Physiological Society
PHARMACOLOGICAL AND SYNAPTIC ACTIVATION OF MGLUR5 INDUCE SPIKE AFTERDEPOLARIZATION AND INCREASE THE SPIKE DISCHARGE OF MEDIUM SPINY NEURONS IN THE NUCLEUS ACCUMBENS VIA UPREGULATION OF PERSISTENT NA+ CURRENTS
Abstract number: OC-06
D'ASCENZO1 M, PODDAM1 V, FELLIN2 T, AZZENA1 GB, HAYDON3 P, GRASSI1 C
1Institute of Human Physiology, Medical School, Catholic University "S. Cuore", Rome
2Italian Institute of Technology, Genoa; (Italy)
3Department of Neuroscience, Tufts University, Boston, MA, (USA)email@example.com
Aim of the present study was to evaluate the impact of mGluR5 activation on neuronal excitability in the nucleus accumbens (NAc).
Bath application of the class I mGluR agonist DHPG (40 mM) to NAc slices significantly increased the number of action potentials elicited by depolarizing stimuli in medium spiny neurons (MSNs). Similar results were obtained when mGluR5 were activated by stimulating glutamatergic afferents to NAc. These effects were abolished by the selective mGluR5 antagonist MPEP (50 mM).
When stimulation protocols eliciting spike afterpotentials were used, both pharmacological and synaptic activation of mGluR5 induced a slow afterdepolarization (ADP) which, in voltage-clamp experiments, was recorded as a slowly inactivating inward current. The ADP was elicited by mGluR5 stimulation via G-protein-dependent activation of phospholipase C and [Ca2+]i increases. The ADP amplitude and spike aftercurrents were significantly reduced by slice pre-incubation with 20 nM TTX or 10 mM riluzole that selectively block persistent Na+ currents (INaP). mGluR5 activation also significantly increased INaP, and the pharmacological blockade of this current prevented the mGluR5-induced enhancement of spike discharge. Our findings suggest that mGluR5 activation upregulates INaP in MSNs of the NAc, thereby inducing an ADP that results in enhanced MSN excitability. These data indicate a novel mechanism by which mGluR5 activation may mediate certain aspects of drug-induced behaviors.
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Acta Physiologica 2009; Volume 197, Supplement 672 :OC-06