Examine the Local Glucose Dynamics in Activity-Induced Hippocampal Neurogenesis

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.