While the similarities between Girk1−/− and Girk2−/− mice with respect to adaptations relevant to excitatory neurotransmission are striking, some differences were evident. Notably, sEPSC amplitudes measured in VTA DA neurons were greater in Girk2−/− mice as compared to Girk1−/− mice. Similarly, mEPSC frequency and amplitude were both significantly elevated in NAcc medium spiny neurons in Girk2−/− mice relative to Girk1−/− mice. These differences may result directly from the loss of Girk signaling in VTA DA neurons, or may reflect more global differences linked to the relative impact of Girk1 and Girk2 ablation on neuronal physiology. While the genetic ablation of Girk1 and Girk2 yields similar outcomes in terms of somatodendritic currents in hippocampal pyramidal, locus ceruleus, and spinal cord dorsal horn neurons (Koyrakh et al. 2005; Marker et al. 2006; Cruz et al. 2008), Girk2 ablation may have a more dramatic impact than Girk1 ablation on synaptic Girk currents, which likely account for a small fraction of the somatodendritic currents measured in most studies. In support of this contention, a significant fraction of Girk2 protein, but not Girk1, is found
