Dopamine modulation of GABA tonic conductance in striatal output neurons

Abstract

We previously reported greater GABA A receptor-mediated tonic currents in D 2+ striatopallidal than D 1 + striatonigral medium spiny neurons (MSNs) are mediated by α5-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 δ-subunit knock-out mice demonstrate that while MSNs in wild-type mice do express δ-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 D 2+ neurons, there was no effect in D 1+ neurons. However, with internal PKA application or dopamine modulation, D 1+ neurons expressed tonic conductance and responded to etomidate application. Our results suggest that distinct phosphorylation of β3-subunits may cause larger tonic current in D 2+ striatopallidal MSNs, and proper intracellular conditions can reveal tonic current in D 1 + cells. Copyright © 2009 Society for Neuroscience.