Dynamic Neurovascular Coupling in Activity-Induced Hippocampal Neurogenesis

Newborn dentate granule cells (DGCs) are continuously generated in the adult brain. These cells integrate into the pre-existing circuit and participate in hippocampus-engaged behaviors. The mechanism underlying how the adult brain governs hippocampal neurogenesis remains poorly understood. In this proposal, we investigate how coupling of pre-existing neurons to the cerebrovascular system regulates hippocampal neurogenesis. Using a new in vivo imaging method in freely moving mice, we found that hippocampus-engaged behaviors such as exploration in a novel environment rapidly increased microvascular blood flow velocity in the dentate gyrus. We will examine whether blocking this exploration-elevated blood flow dampens experience-induced hippocampal neurogenesis. We next propose to examine what molecules mediate neurovascular coupling network in the dentate gyrus to regulate experience-induced neurogenesis in the adult brain. The findings will provide a novel path to understand how adult brain actively control the number of newborn dentate granule cells. It will also provide a novel approach for analyzing dynamic neurovascular coupling during behaviors and pathological conditions including Alzheimer disease and aging.