NRSA for Rachel Elizabeth Kery: The Role of Adult-Born Dentate Granule Cells in Influencing C3 Neuronal Activity

Project Summary The hippocampus, a brain structure critical for learning and memory, is one of just two brain areas (along with the olfactory bulb) that continue to add new neurons throughout adult life. The continual addition of new neurons, known as adult neurogenesis, is disrupted in a variety of neuropsychiatric disorders, including major depressive disorder, and post-traumatic stress disorder. While adult-born neurons are still immature, they contribute to several learning and memory functions, including certain forms of spatial memory. The integration of these new neurons into already existing circuits within the hippocampus appears to be necessary for healthy hippocampal function, but the process by which these immature adult-born neurons affect activity in downstream hippocampal regions is poorly understood. I have developed a novel anterograde labeling construct that will allow me to investigate the process, and functional consequences of integration of adult-born neurons into already existent circuits. I have demonstrated in my preliminary studies that I am able to label the anterograde synaptic connections with high fidelity. In this proposal, I present two queries I intend to use my construct to pursue: (1) how activity (or lack of activity) of adult-born hippocampal neurons affects downstream circuit activity in the hippocampus, and (2) whether neuro- glial coupling is involved in mediating this effect. Understanding how adult-born neurons influence downstream activity of already existent circuits is essential for developing new interventions for hippocampal disease, as well as for normal age-related cognitive decline. Results from this study will allow for greater insight for the development of new therapies for a variety of neuropsychiatric conditions.