We hypothesized that VTA DA neurons in Girk2−/− mice receive elevated inhibitory input from local GABA interneurons. To test this hypothesis, we first recorded spontaneous inhibitory postsynaptic currents (sIPSCs) in VTA DA neurons from wild-type and Girk−/− mice (Fig. 3). The frequency and amplitude of sIPSCs measured in wild-type mice were consistent with previous reports (Mathon et al. 2005). Consistent with our prediction, sIPSC frequency was elevated in DA neurons from Girk2−/− mice, relative to frequencies measured in wild-type, Girk1−/−, and Girk3−/− mice (Fig. 3A,B). sIPSC amplitudes did not differ across genotypes (Fig. 3C). Second, we examined the impact of picrotoxin on the spontaneous activity of VTA DA neurons in slices from wild-type and Girk−/− mice, reasoning that GABAA receptor blockade should normalize firing rates if the lower basal firing rates seen in Girk2−/− mice were attributable to elevated GABAergic input. Indeed, VTA DA neuron firing rates did not differ across genotypes in the presence of picrotoxin application (Fig. 3D).
