Functional networks activated by controllable and uncontrollable stress in male and female rats

The ability of an individual to reduce the intensity, duration or frequency of a stressor is a critical determinant of the consequences of that stressor on physiology and behavior. To expand our understanding of the brain networks engaged during controllable and uncontrollable stress and to identify sex differences, we used functional connectivity analyses of the immediate early gene product Fos in male and female rats exposed to either controllable or uncontrollable tail shocks. Twenty-eight regions of interest (ROI) were selected from the structures previously evinced to be responsible for stress response, action-outcome learning, or sexual dimorphism. We found that connectivity across these structures was strongest in female rats without control while weaker connectivity was evident in male rats with control over stress. Interestingly, this pattern correlates with known behavioral sex differences where stressor controllability leads to resilience in male but not female rats. Graph theoretical analysis identified several structures important to networks under specific conditions. In sum, the findings suggest that control over stress reshapes functional connectivity.