JHIBRG:Abstract October 4 2007

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Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain

Adult neurogenesis occurs throughout life in discrete regions of the adultmammalian brain. Little is known about the mechanism governing the sequential developmental process that leads to integration of new neurons from adult neural stem cells into the existing circuitry. The role of Disrupted-In-Schizophrenia1 (DISC1), a schizophrenia susceptibility gene, in adult hippocampal neurogenesis will be discussed. Unexpectedly,downregulation of DISC1 leads to acceleratedneuronal integration, resulting in aberrant morphological development and mispositioning of new dentate granule cells in a cell-autonomous fashion. Functionally, newborn neurons with DISC1 knockdown exhibit enhanced excitability and accelerated dendritic development and synapse formation. Furthermore, DISC1 cooperates with its binding partner NDEL1 and Fez1 in regulating adult neurogenesis.