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

成年哺乳动物大脑的神经干细胞在整个生命过程中产生神经元，并且全世界都投入了巨大的努力来理解成年神经发生的生理作用，并操纵该过程以开发神经退行性疾病的新疗法。然而，神经干细胞在体内难以扩增，其向神经发生的转化难以控制，是阻碍这些研究的主要障碍之一。事实上，还没有系统报道允许神经干细胞的有条件和时间控制的扩增最终增加成人大脑中的神经元输出。在这种情况下，在我们的实验室最近的观察表明，这样的操作可以在成年小鼠海马通过一个短暂的过表达的特定的细胞周期调节。因此，我们将在这里评估的生存和功能整合的大脑回路的条件下产生的神经元，这可能构成一个重要的基础，为进一步研究解决成人神经发生的生理作用的认知功能，如学习和记忆，或促进脑损伤或神经退行性疾病后恢复。

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.