Given the differential expression patterns of Girk1 and Girk2 in midbrain DA neurons, the comparable profiles for Girk1−/− and Girk2−/− mice with respect to basal and cocaine-induced motor activity argue that the loss of Girk signaling in these neurons is not the primary cause. Thus, we asked next whether Girk ablation altered other aspects of midbrain DA neuron physiology. We first examined the impact of Girk subunit ablation on the spontaneous activity and afferent input to putative DA neurons in acutely-isolated slices of the VTA. VTA DA neurons were identified using morphological and electrophysiological criteria (Materials and Methods) that we demonstrated previously correlated well with expression of Pitx3 (Labouebe et al. 2007), a DA neuron-specific transcription factor. These criteria also correlated well with robust GABABR-dependent somatodendritic outward currents in slices from wild-type mice (Fig. 2A). Peak outward currents evoked by the GABABR agonist baclofen measured in slices from Girk1−/− and Girk3−/− mice were indistinguishable from wild-type, whereas currents in slices from Girk2−/− mice were dramatically attenuated (Fig. 2A,B).
