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.

Public Health Relevance

The process by which immature adult-born hippocampal neurons influence downstream hippocampal activity is poorly understood. Using a novel anterograde trans-synaptic viral labeling construct I have developed, I will examine how activity of immature adult-born hippocampal neurons influence downstream hippocampal activity, and explore a possible role of neuro-glial signaling in mediating this effect.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH116650-03
Application #
9988919
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Driscoll, Jamie
Project Start
2018-09-05
Project End
2022-09-04
Budget Start
2020-09-05
Budget End
2021-09-04
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794