First, our study represents one of the first attempts to dissect the molecular interaction between extrinsic niche signaling and intrinsic regulators of neurogenesis in the mammalian brain. Since its initial discovery as a prominent susceptibility gene for schizophrenia and other major mental illnesses, DISC1 has been shown to regulate multiple neurodevelopmental processes in animal models (Chubb et al., 2008). During adult neurogenesis, DISC1 is thought to function as an intrinsic modulator to constrain stimulating effects of unknown extrinsic mechanisms in maintaining proper neurogenesis. Here we showed that DISC1 gates signaling from GABA-induced depolarization in regulating dendritic growth during adult neurogenesis. During early postnatal neurogenesis, extending the period of GABAergic depolarization through KCC2 KD leads to further enhancement of dendritic growth with concurrent DISC1 KD, whereas DISC1 KD alone has minimal effect. Therefore, DISC1 appears to be specifically recruited during periods of neuronal development driven by prolonged GABA-mediated depolarization. Multiple neurotransmitters, including GABA, have been shown to activate the AKT pathway through Ca2+ signaling (Yano et al., 1998). Using a series of genetic, pharmacological and immunohistological approaches, we provided evidence supporting
