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Chunk #20 — RESULTS — Extending Period of Depolarizing GABA Signaling Restores DISC1-dependent Regulation of Early Postnatal Hippocampal Neurogenesis

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Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.
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We next examined the effect of DISC1 KD on newborn neurons with an extended period of GABA-induced depolarization during early postnatal neurogenesis. Interestingly, co-expression of shRNA-D1/DsRed and shRNA-K2/GFP led to a significant further increase of dendritic growth of new neurons than shRNA-K2 expression alone at 7 dpi (Figures 5A to 5C and S5A). Importantly, the increased dendritic growth from shRNA-K2 expression with or without shRNA-D1 was abolished by mTOR inhibition with rapamycin (Figures 5D and S5E), similar to what occurs during adult neurogenesis with DISC1 KD (Kim et al., 2009), suggesting a shared molecular mechanism. On the other hand, there were no apparent effects on soma size, number of primary dendrites, or positioning of newborn neurons under any conditions (Figure S5).