Elevated inhibitory input to, and lower ex vivo firing rates of, VTA DA neurons in Girk2−/− mice is inconsistent with the DA-related phenotypes shown in Fig. 1 and reported previously (Blednov et al. 2001; Blednov et al. 2002; Morgan et al. 2003). We reasoned that Girk2 ablation may also trigger adaptations facilitating excitatory neurotransmission in VTA DA neurons, and that the influence of these adaptations would be muted due to the transection of excitatory afferents that occurs during slice preparation. To address this possibility, we first measured spontaneous excitatory postsynaptic currents (sEPSCs) in VTA DA neurons from wild-type and Girk−/− mice (Fig. 4). sEPSCs were readily observed in VTA DA neurons from wild-type mice (Fig. 4A), with amplitudes and frequencies consistent with previous reports using similar conditions (Engblom et al. 2008; Zweifel et al. 2008). sEPSC frequency was elevated significantly and similarly in VTA DA neurons from Girk1−/− and Girk2−/− mice, but not Girk3−/− mice (Fig. 4B). Interestingly, sEPSC amplitudes were elevated significantly in Girk2−/− mice (Fig. 4C).
