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The Journal of Neuroscience, April 22, 2009, 29(16):5116-5126; doi:10.1523/JNEUROSCI.4737-08.2009

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Cellular/Molecular
Dopamine Modulation of GABA Tonic Conductance in Striatal Output Neurons

Megan J. Janssen,^1,2 Kristen K. Ade,^1,3 Zhanyan Fu,¹ and Stefano Vicini^1,2

¹Department of Physiology and Biophysics, ²Department of Pharmacology, and ³Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC 20007

Correspondence should be addressed to Megan J. Janssen, Department of Physiology and Biophysics, BSB230 Georgetown University School of Medicine, 3900 Reservoir Road, Washington, DC 20007. Email: mjj34{at}georgetown.edu

We previously reported greater GABA_A receptor-mediated tonic currents in D₂+ striatopallidal than D₁+ striatonigral medium spiny neurons (MSNs) are mediated by 5-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 -subunit knock-out mice demonstrate that while MSNs in wild-type mice do express -subunit-containing receptors, this receptor subtype is not responsible for tonic conductance observed in the acute slice preparation. We assessed the contribution of the β1- and β3-subunits expressed in MSNs by their sensitivity to etomidate, an agonist selective for β2- or β3-subunit-containing GABA_A 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 β3-subunits may cause larger tonic current in D₂+ striatopallidal MSNs, and proper intracellular conditions can reveal tonic current in D₁+ cells.

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Received Oct. 1, 2008; revised Feb. 17, 2009; accepted March 19, 2009.

Correspondence should be addressed to Megan J. Janssen, Department of Physiology and Biophysics, BSB230 Georgetown University School of Medicine, 3900 Reservoir Road, Washington, DC 20007. Email: mjj34{at}georgetown.edu

This article has been cited by other articles:

				D. Belelli, N. L. Harrison, J. Maguire, R. L. Macdonald, M. C. Walker, and D. W. Cope Extrasynaptic GABAA Receptors: Form, Pharmacology, and Function J. Neurosci., October 14, 2009; 29(41): 12757 - 12763. [Abstract] [Full Text] [PDF]

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