Persistent elevation in glutamatergic signaling in VTA DA neurons can trigger adaptations in the NAcc, including increased glutamatergic input, dendritic spine density, and expression of the AMPA receptor subunit GluR1 (Robinson and Kolb 2004; Boudreau and Wolf 2005; Pulipparacharuvil et al. 2008; Mameli et al. 2009). Given the evidence for increased glutamatergic neurotransmission in VTA DA neurons from Girk1−/− and Girk2−/− mice, we next probed for adaptations related to excitatory neurotransmission in the NAcc of these mice. Specifically, we measured miniature EPSCs (mEPSCs) in NAcc shell neurons from wild-type and Girk−/− mice (Fig. 6). We found that mEPSC frequency and amplitude were elevated in NAcc neurons from Girk1−/− and Girk2−/− mice, relative to wild-type controls. Interestingly, mEPSC frequency and amplitude were significantly higher in NAcc neurons from Girk2−/− mice as compared to neurons from Girk1−/− mice.
