Adaptation to Stress Switches Stress-Evoked Network Disconnection to a New Forebrain Network State.

Stress adaptation is critical to maintaining mental and physical health. If acute stress is associated with changes in neuronal activity in many brain regions, how neuronal activity itself is coordinated across regions during stress and how neuronal networks are modified during stress adaptation are unknown. In male rats, we recorded local field potentials (LFPs) from stress-responsive regions, including the prelimbic cortex, anterior cingulate cortex, basolateral amygdala, lateral habenula, and dorsal hippocampus, in rats during repeated stress exposure in a within-subjects design. We characterized network activity by computing cross-region coherence, Granger causality, and phase-amplitude coupling on bipolar derivatives of LFPs. We established a stress adaptation model in rats: the behavioral response to acute 10 min restraint stress returned to baseline after a second restraint 3 h later. The pre-stress state was characterized by robust global network interactions in the theta and gamma bands. The first exposure induced widespread disconnection, whereas following the second one, when rats showed an adaptive response, the connectivity pattern appeared different from that of the pre-stress state. Finally, baseline, stressed, and adaptive states were predicted (>90% accuracy) from network activity. Overall, we showed that the acutely stressed brain state was primarily a state of network disconnection, while stress adaptation was a new network state rather than a return to baseline.