VTA DA neurons receive inhibitory inputs from local and projection GABA neurons (Floresco et al., 2003; Jhou et al., 2009; Padgett et al., 2012). Because activation of GABABR-GIRK currents in VTA is sufficient to inhibit phasic firing of DA neurons (Seutin et al., 1994), we wondered whether the reduced GABABR-activated GIRK current would be sufficient to alter inhibitory control of neuronal activity. We constructed input-output curves for induced firing measured in current-clamp mode for wild-type and SNX27DA KO DA neurons (Figure 3). Remarkably, a saturating concentration of baclofen (300 µM) failed to inhibit firing induced over a range of current injections in DA neurons of SNX27DA KO mice, in contrast to wild-type controls (Figure 3A–D).
