Examine the local glucose dynamics in activity-induced hippocampal neurogenesis

摘要 这项提案的总体目标是探索调节活动的局部细胞葡萄糖动力学- 诱导海马神经发生。海马神经发生对生理， 行为的，不幸的是也有病理的刺激。它一直是并将继续是一个重要的 问：无论是生理刺激还是病理刺激，大脑活动如何调节 以及成年大脑中新海马神经元的电路整合。在这个探索性的提议中， 大脑主动调节局部葡萄糖动力学以响应大脑刺激，并最终调节 将研究神经发生。已经提出了两组实验。1)检查局部血糖 在校园活动中的动态。齿状回星形胶质细胞的葡萄糖动力学 将确定在上下文探索期间的脑回。将测量星形胶质细胞中的葡萄糖水平 以真实的时间方式在常规的和增强的探测行为期间。细胞间运输 将检查齿状回中葡萄糖衍生的代谢物乳酸的机制。2)确定角色 局部葡萄糖动力学在调节活动诱导的海马神经发生。的潜在影响 将测试齿状回中葡萄糖动力学对新海马神经元存活的影响。葡萄糖 星形胶质细胞或神经祖细胞的转运蛋白将被敲除， 将测试神经元。这些发现最终将为理解细胞如何 葡萄糖动力学变化的反应，以校园参与的行为和葡萄糖动力学如何 解释了活动诱导的海马神经发生。

Abstract The overall goal of this proposal is to explore the local cellular glucose dynamics in regulating activity- induced hippocampal neurogenesis. Hippocampal neurogenesis sensitively responds to physiological, behavioral, and unfortunately also pathological stimuli. It has been and is continuously being an essential question: how brain activities, no matter they are physiological or pathological stimuli, regulate the generation and circuit integration of new hippocampal neurons in the adult brain. In this explorative proposal, how adult brain actively regulates the local glucose dynamics in response to brain stimuli and eventually regulates neurogenesis will be studied. Two sets of experiments have been proposed. 1) Examine the local glucose dynamics during the hippocampus-engaged behaviors. The glucose dynamics in the astroglia of the dentate gyrus during the contextual exploration will be determined. The level of glucose in astroglia will be measured in real time manner during the regular and enhanced exploration behavior. The intercellular transportation machinery of glucose-derived metabolite, lactate, in the dentate gyrus will be examined. 2) Determine the role of local glucose dynamics in regulating activity-induced hippocampal neurogenesis. The potential effect of glucose dynamics in the dentate gyrus on the survival of new hippocampal neurons will be tested. The glucose transporters of astroglial cells or neural progenitors will be knocked down and the survival of newly generated neurons will be tested. The findings will ultimately provide insights into the understanding of how the cellular glucose dynamics change in response to hippocampus-engaged behaviors and how the glucose dynamics account for the activity-induced hippocampal neurogenesis.