Imaging adult-born neurons in action using head-mounted minimicroscopes

项目总结/文摘

Project Summary/Abstract The hippocampus is one of a select few brain regions that retain the ability to generate neurons in adulthood. Research in human patients and animal models suggests that increases and decreases in neurogenesis alter memory function and contribute to the etiology and treatment of emotional disorders. Despite almost 15 years of research linking adult neurogenesis to memory and emotional regulation, almost nothing is known about the circuit and coding mechanisms through which adult neurogenesis influences these processes. The recent development (with BRAIN Initiative support) of head-mounted minimicroscopes provides an unprecedented opportunity to image activity of adult-born neurons as animals learn and behave. Under this award, we will acquire equipment and training that will enable our lab to sustainably incorporate miniscope imaging into our research program on adult neurogenesis. In addition, we will perform calcium imaging experiments in freely moving mice as they explore contexts and undergo contextual fear conditioning, a model learning paradigm that is sensitive to perturbations of adult neurogenesis. Using optogenetic silencing of adult-born neurons, we will characterize how adult-born neurons influence coding of context memory in dentate gyrus, a region required for context memory. These experiments will provide new and previously unattainable insights into the mechanisms through which adult-born neurons regulate hippocampal memory, and they will enable our lab to integrate miniscope technology in a sustainable way in multiple ongoing research streams.