Coping switches stress evoked network disconnection to a new forebrain network state.

Coping with stress is critical to maintaining mental and physical health. Acute stress is associated with changes in neuronal activity across many brain regions and with the reorganization of cross- region correlations in neurovascular coupling. How neuronal activity itself is coordinated across regions during stress, and how neuronal networks are modified during coping, are unknown. We recorded in rats local field potentials (LFPs) simultaneously from five stress-responsive regions during stress and stress-coping behavior. We characterized network activity by computing cross- region coherence, Granger causality, and phase-amplitude coupling on bipolar derivatives of LFPs in the lateral habenula, basolateral amygdala, dorsal hippocampus, prelimbic cortex, and anterior cingulate cortex. First, we established a stress-coping model in rats. We showed that the behavioral response to acute 10-minute restraint stress returned to baseline after a second restraint 3 hours later. The pre-stress state was characterized by robust global network interactions in the theta (6- 9 Hz) and gamma (45-65 Hz) bands. Stress exposure led to nearly complete loss of connectivity. During coping, the robust connectivity reemerged, but in a new pattern compared to the pre-stress state. Finally, we found that baseline, stressed, and coping states can be predicted with high accuracy (> 90 %) from network activity. Overall, we showed that the acutely stressed brain state was primarily a state of network disconnection, while coping was a new network state rather than a return to baseline.