Dopamine Modulation of GABA Tonic Conductance in Striatal Output Neurons

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Abstract
We previously reported greater GABAAreceptor-mediated tonic currents in D2+ striatopallidal than D1+ 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 GABAAreceptors. 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.