Survival and Integration of Newborn Hippocampal Neurons upon Inducible Expansion of Neural Stem Cells

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Neural stem cells of the adult mammalian brain generate neurons throughout life and great efforts are invested worldwide to understand the physiological role of adult neurogenesis and to manipulate this process for developing novel therapies of neurodegenerative disease. However, as one major obstacle hampering these studies, neural stem cells in vivo revealed difficult to expand and their switch to neurogenesis hard to control. In fact, no system has yet been reported that allows the conditional and temporally-controlled expansion of neural stem cells to ultimately increase the neuronal output in the adult brain. In this context, recent observations in our laboratory indicate that such manipulation can be performed in the adult mouse hippocampus by a transitory overexpression of specific cell cycle regulators. Thus, we will here assess the survival and functional integration in the brain circuitry of the conditionally generated neurons, which may constitute an important basis for further studies addressing the physiological role of adult neurogenesis on cognitive functions, such as in learning and memory, or to promote brain recovery upon injury or neurodegenerative disease.