Hippocampal activity influences neurogenesis in the adult dentate gyrus; however, little is known about the involvement of the hippocampal circuitry in this process. In the subgranular zone of the adult dentate gyrus, neurogenesis involves a series of differentiation steps from radial glia-like stem/progenitor (type-1) cells, to transiently amplifying neuronal progenitor (type-2) cells, to postmitotic neurons. In this study, we conducted GFP-targeted recordings of progenitor cells in fresh hippocampal slices from nestin-GFP mice and found that neuronal progenitor (type-2) cells receive active direct neural inputs from the hippocampal circuitry. This input was GABAergic but not glutamatergic. The GABAergic inputs depolarized type-2 cells because of their elevated [Cl(-)](i). This excitation initiated an increase of [Ca(2+)](i) and the expression of NeuroD. A BrdU-pulse labeling study with GABA(A)-R agonists demonstrated the promotion of neuronal differentiation via this GABAergic excitation. Thus, it appears that GABAergic inputs to hippocampal progenitor cells promote activity-dependent neuronal differentiation.

We have found in the adult rat that the persistent expression of a highly polysialylated neural cell adhesion molecule (NCAM-H) that is generally specific to developing tissues, remains restrictively in the cells of the deepest portion of the dentate granular layer. Since the granule cells are known to continue to be generated in this region during the adult period, we have tried to determine whether NCAM-H is expressed by newly generated granule cells. Immunoelectron microscopic observation revealed that about half of the NCAM-H-expressing cells had the features of dentate granule cells, and that the rest of these cells appeared to be immature cells. Double immunostaining for NCAM-H and glial fibrillary acidic protein (GFAP) revealed that the NCAM-H-expressing cells differed from GFAP-positive glial cells. In rats injected with 5-bromo-2'-deoxyuridine (BrdU) at post-natal day 35, double immunostaining for NCAM-H and BrdU demonstrated that the BrdU-labeled cells expressed NCAM-H at 12 d after the injection but not at 80 d. These results provide the first direct evidence that NCAM-H is expressed transiently by newly generated granule cells that may add new neuronal circuits to the adult hippocampal formation.

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Disrupted-In-Schizophrenia 1 (DISC1), a susceptibility gene for major psychiatric disorders, regulates neuronal migration and differentiation during mammalian brain development. Although roles for DISC1 in postnatal neurogenesis in the dentate gyrus (DG) have recently emerged, it is not known how DISC1 and its interacting proteins govern the migration, positioning, and differentiation of dentate granule cells (DGCs). Here, we report that DISC1 interacts with the actin-binding protein girdin to regulate axonal development. DGCs in girdin-deficient neonatal mice exhibit deficits in axonal sprouting in the cornu ammonis 3 region of the hippocampus. Girdin deficiency, RNA interference-mediated knockdown, and inhibition of the DISC1/girdin interaction lead to overextended migration and mispositioning of the DGCs resulting in profound cytoarchitectural disorganization of the DG. These findings identify girdin as an intrinsic factor in postnatal development of the DG and provide insights into the critical role of the DISC1/girdin interaction in postnatal neurogenesis in the DG.