Researcher |Research Overview
Even a single traumatic experience can trigger the onset of a negatively valenced affective state that persists for days to weeks. Adaptive properties of such states include hyperarousal and heightened vigilance, but their excessive duration and/or severity can lead to pathological conditions such as post-traumatic stress disorder (PTSD) and severe depression. What are the neural and molecular substrates responsible for the induction, persistence and severity of such states? Why do even genetically identical individuals show differential susceptibility to mood disorders precipitated by stress? Can specific pharmacological or genetic manipulations be developed in the lab that can prevent or reverse stress-induced psychiatric disorders in people?
We are addressing these questions by focusing on the lateral septal (LS) node of the septohippocampal system, a pathway long implicated in the control of stress-induced behavioral states but which has received relatively little attention in the modern era. Although often overlooked, the LS is likely to play critical roles in human affective disorders as it is robustly activated by stressful stimuli and required for persistent behavioral responses to stress (e.g. increased anxiety). However, the LS is a large, highly heterogeneous structure containing tens if not hundreds of distinct cell types that also mediate other, apparently disparate behavioral functions (e.g. social behavior, drug abuse, sexual pleasure). Which specific neuronal or glial populations subserve which functions via which pathways remains virtually unknown.
To target defined components of LS stress circuitry, we are taking a genetic approach that combines mouse molecular genetics, viral vectors, behavioral analysis, calcium imaging, and electrophysiological approaches to causally link the activity of specific circuits and/or genes to the persistent behavioral effects of stress.