Document Detail


BK channels mediate dopamine inhibition of firing in a subpopulation of core nucleus accumbens medium spiny neurons.
MedLine Citation:
PMID:  25219484     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Dopamine, a key neurotransmitter mediating the rewarding properties of drugs of abuse, is widely believed to exert some of its effects by modulating neuronal activity of nucleus accumbens (NAcc) medium spiny neurons (MSNs). Although its effects on synaptic transmission have been well documented, its regulation of intrinsic neuronal excitability is less understood. In this study, we examined the cellular mechanisms of acute dopamine effects on core accumbens MSNs evoked firing. We found that 0.5µM A-77636 and 10µM quinpirole, dopamine D1 (DR1s) and D2 receptor (D2Rs) agonists, respectively, markedly inhibited MSN evoked action potentials. This effect, observed only in about 25% of all neurons, was associated with spike-timing-dependent (STDP) long-term potentiation (tLTP), but not long-term depression (tLTD). Dopamine inhibits evoked firing by compromising subthreshold depolarization, not by altering action potentials themselves. Recordings in voltage-clamp mode revealed that all MSNs expressed fast (IA), slowly inactivating delayed rectifier (Idr), and large conductance voltage- and calcium-activated potassium (BKs) channels. Although A-77636 and quinpirole enhanced IA, its selective blockade by 0.5µM phrixotoxin-1 had no effect on evoked firing. In contrast, exposing tissue to low TEA concentrations and to 10µM paxilline, a selective BK channel blocker, prevented D1R agonist from inhibiting MSN firing. This result indicates that dopamine inhibits MSN firing through BK channels in a subpopulation of core accumbens MSNs exclusively associated with spike-timing-dependent long-term potentiation.
Authors:
Xincai Ji; Gilles E Martin
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Publication Detail:
Type:  Journal Article     Date:  2014-09-16
Journal Detail:
Title:  Brain research     Volume:  1588     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-02     Completed Date:  -     Revised Date:  2014-12-04    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-16     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Elsevier B.V. All rights reserved.
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Grant Support
ID/Acronym/Agency:
R01 AA020501/AA/NIAAA NIH HHS

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