To directly examine whether intrinsic DISC1 interacts with extrinsic GABA signaling in regulating new neuron development, we used a double knockdown strategy with two retroviruses: one co-expressing shRNA-NK1 and GFP and the other co-expressing shRNA-D1 and DsRed (Figure 1C). GFP+DsRed+ new neurons exhibited similar dendritic growth as those expressing shRNA-C1 at 14 dpi (Figures 1D and S1D). In contrast, other defects from DISC1 KD were not rescued by shRNA-NK1 expression (Figures S1A to S1C). To ensure that GABA, but not Cl− signaling, is required for DISC1-dependent regulation of newborn neurons, we developed specific shRNA against the γ2 subunit of GABAARs (shRNA-γ2; Figures S1E to S1F), a critical subunit involved in GABA signaling. Expression of shRNA-γ2 in newborn neurons rescued the DISC1 KD-induced acceleration of dendritic growth (Figures 1D and S1D), but not other defects (Figures S1A to S1C). To identify the mechanistic link between GABA and DISC1 signaling, we examined AKT, a DISC1 target, and subsequent mTOR activation in newborn neurons (Kang et al., 2011; Kim et al., 2009). Interestingly, DISC1 KD-induced increases of pAKT and pS6 levels were significantly
