PROJECT SUMMARY Over 40 millions individuals in the United States are impacted by stress related disorders, that are highly comorbid with mood disorders such as anxiety and depression. Cognitive behavioral therapy and decades of animal literature has established that reinstating a sense of autonomy or behavioral control over a stressful experience can buffer many of the psychological and behavioral impacts of stress and reduce the severity of depressive and anxiety-like behaviors. However, it is not entirely known which neurochemical pathways are recruited by behavioral control to facilitate or hinder this stress resilience. Understanding how neurochemical signaling dynamics change following stress (with and without behavioral control) and identifying which projections are responsible for these changes is a foundational step in developing therapeutics for stress related disorders. To address this, I will implement a rodent model of stressor controllability to 1) identify how neurochemical signaling dynamics change following behavioral control, in a brain region highly implicated in mediating the effects of stress and 2) manipulate neurochemical-specific projections to this region that are implicated in these changes to identify their involvement in stressor controllability. The goal of the proposed project is to determine how behavioral control impacts discrete neurochemical signaling specifically between the lateral habenula (LHb) and the ventral tegmental area (VTA), two interacting brain regions that play causal roles in both stress and motivated behavior. The successful completion of these aims will address mechanistically how behavioral control influences LHb neurochemical signaling and test the hypothesis that the VTA glutamate → LHb pathway contributes to behavioral deficits following stress experience in the absence of behavioral control.