title: Dopamine modulation of GABA tonic conductance in striatal output neurons.
abstract: We previously reported greater GABAA receptor-mediated tonic currents in D2+ striatopallidal than D1+ striatonigral medium spiny neurons (MSNs) are mediated by alpha5-subunit-containing receptors. Here, we used whole-cell recordings in slices from bacterial artificial chromosome transgenic mice to investigate the link between subunit composition, phosphorylation, and dopamine receptor activation. Whole-cell recordings in slices from delta-subunit knock-out mice demonstrate that while MSNs in wild-type mice do express delta-subunit-containing receptors, this receptor subtype is not responsible for tonic conductance observed in the acute slice preparation. We assessed the contribution of the beta1- and beta3-subunits expressed in MSNs by their sensitivity to etomidate, an agonist selective for beta2- or beta3-subunit-containing GABAA receptors. Although etomidate produced substantial tonic current in D2+ neurons, there was no effect in D1+ neurons. However, with internal PKA application or dopamine modulation, D1+ neurons expressed tonic conductance and responded to etomidate application. Our results suggest that distinct phosphorylation of beta3-subunits may cause larger tonic current in D2+ striatopallidal MSNs, and proper intracellular conditions can reveal tonic current in D1+ cells.
authors.affiliation: Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC 20007, USA. mjj34@georgetown.edu
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Janssen
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Ade
authors.forename: Zhanyan
authors.initials: Z
authors.lastname: Fu
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicini
mesh_terms: D000818:Animals; D002460:Cell Line; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009431:Neural Conduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
chemical_list: D018491:Dopamine Agonists; C546273:GABRB3 protein, human; C546270:Gabrb3 protein, mouse; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D004298:Dopamine