To examine whether DISC1 and GABA signaling interacts during adult neurogenesis, we first characterized the time-course of neuronal development regulated by these two pathways. To knockdown DISC1 specifically in adult-born new neurons, engineered retroviruses co-expressing GFP and a previously characterized shRNA against mouse disc1 (shRNA-DISC1#1; shRNA-D1) were stereotaxically injected into the dentate gyrus at postnatal day 42 (P42; See Experimental Procedures) (Duan et al., 2007). shRNA-D1/GFP+ neurons exhibited accelerated dendritic growth compared with those expressing a control shRNA (shRNA-C1) at 14 days post viral injection (dpi; Figure 1A), as well as soma hypertrophy, ectopic primary dendrites and aberrant positioning as previously reported (Figures S1A to S1C) (Duan et al., 2007). Interestingly, the effect of DISC1 KD on newborn neurons, including increased dendritic length and complexity, manifested only after 7 dpi (Figures 1B and S1D). We previously showed that expression of a specific shRNA against mouse nkcc1 (shRNA-NK1) abolishes GABA-induced depolarization of newborn neurons in the adult hippocampus (Ge et al., 2006). Consistent with a critical role of depolarizing GABA signaling in adult neurogenesis, shRNA-NK1+/GFP+ new neurons exhibited significant decreases in
