Major depressive disorder (MDD) is a mental disorder characterized by a depressed mood, diminished interests, impaired cognitive function, and vegetative symptoms, such as disturbed sleep or appetite. Some of the MDD symptoms can be remedied using antidepressants; however, 30% of individuals do not respond to the available antidepressants, and most patients experience severe side effects. The cellular and molecular mechanisms that underlie MDD are still largely unknown. In this project, we identify a novel biological mechanism that underlies MDD and involves stress-induced communication between neurons and glial cells. Based on our unpublished data, we hypothesize that neurons communicate with glial cells to drive depression-like behavior in a murine model of MDD. In this study, we intend to use novel and cutting-edge methods to elucidate this crosstalk. In my research, I will uncover how this stress-induced crosstalk shapes the hippocampal circuit and codes depressive-like behavior. Using mouse models, behavioral tests, genetic manipulations, spatial transcriptomics, and immunohistochemistry, I will uncover the mechanism that will pave the way to improved, targeted therapies for MDD.

Supervisor: Dr. Gali Umschweif-Nevo