BK channels mediate dopamine inhibition of firing in a subpopulation of core nucleus accumbens medium spiny neurons
The Brudnick Neuropsychiatric Research Institute, Department of Psychiatry; Martin Lab
Neuroscience and Neurobiology
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 0.5 microM A-77636 and 10 microM 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 0.5 microM phrixotoxin-1 had no effect on evoked firing. In contrast, exposing tissue to low TEA concentrations and to 10 microM 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.
BK channels, Dopamine, Mice, Nucleus accumbens, Potassium channels
DOI of Published Version
Brain Res. 2014 Nov 7;1588:1-16. doi: 10.1016/j.brainres.2014.09.015. Epub 2014 Sep 16. Link to article on publisher's site
Ji X, Martin GE. (2014). BK channels mediate dopamine inhibition of firing in a subpopulation of core nucleus accumbens medium spiny neurons. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1016/j.brainres.2014.09.015. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1451