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.
The presence of behavioral control over a stressor can blunt many of the effects of the stressor. We have recently reported that uncontrollable stress (inescapable electric tailshock, IS) reduces later social exploration of a juvenile whereas controllable stress (escapable shock, ES) does not. Activation of the ventral medial prefrontal cortex (vmPFC) is crucial to blunting the effects of IS on later escape behavior (learned helplessness). The goal of the current study was to test the role of the vmPFC in modulating the effects of stressor controllability on anxiety in the social exploration test. Thus, adult male rats were implanted with cannula guides for drug microinjection into the vmPFC. In Experiment 1, temporary inactivation of the vmPFC with the GABA(A) agonist muscimol before exposure to ES prevented the protective effects of stress control, leading to reduced social exploration. In Experiment 2, excitation of the vmPFC prior to IS with the GABA-activated Cl(( - )) channel antagonist picrotoxin mimicked the stress resistance produced by control and prevented IS-induced reduction in social exploration. These results are consistent with prior work and identify the vmPFC as a critical component of the neural circuitry mediating the effects of stressor control on later behaviors. The relationship between the vmPFC, dorsal raphé nucleus, and other structures mediating stress-induced anxiety are discussed.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)