To further assess the functional interaction between DISC1 and GABA signaling during adult neurogenesis, we examined the effect of enhancing GABA signaling on DISC1-dependent regulation of dendritic development in vivo. Our previous time course analysis of different modes of GABA signaling showed that new neurons are initially activated tonically by ambient GABA followed by both tonic and phasic/synaptic GABA activation starting from 7 dpi in the adult brain (Ge et al., 2006). Importantly, both tonic and synaptic activation by GABA remain depolarizing until at least 14 dpi (Ge et al., 2006). In the first experiment, we injected the GABA transaminase inhibitor vigabatrin (25 µg/g body weight per day from 3 to 6 dpi, i.p.) (Wu et al., 2003) to increase tonic GABA signaling in newborn neurons (Figure 2A). shRNA-D1/GFP+ neurons with vigabatrin treatment exhibited a significant increase in total dendritic length at 7 dpi, whereas vigabatrin by itself or expression of shRNA-D1 alone had no effect (Figures 2A to 2B). Co-manipulation also significantly increased pAKT and pS6 levels in newborn neurons more than either manipulation alone (Figures 2C to 2D
