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终生生成神经元，全世界都在投入大量的努力来了解成年神经发生的生理作用，并操纵这一过程来开发神经退行性疾病的新疗法。然而，作为阻碍这些研究的主要障碍之一，体内神经干细胞很难扩增，它们向神经发生的切换也很难控制。事实上，目前还没有任何系统可以允许神经干细胞的有条件和时间控制的扩张最终增加成人大脑中的神经元输出。在这种情况下，我们实验室最近的观察表明，这种操作可以通过特定细胞周期调节因子的短暂过度表达在成年小鼠的海马体中进行。因此，我们将在这里评估条件产生的神经元在大脑回路中的存活和功能整合，这可能构成进一步研究成人神经发生对认知功能的生理作用的重要基础，例如在学习和记忆中，或促进损伤或神经退行性疾病时的大脑恢复。

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.