Adaptive Reorganization of Local Sleep and Prelimbic Cortical Circuits Predict Behavioral Resilience to Social Defeat Stress

Abstract

Understanding the biological mechanisms responsible for resilience to stress—the ability to overcome adverse conditions—remains a major challenge. While sleep is a known regulator of resilience, the localized cortical dynamics that facilitate this process remain unclear. We hypothesized that resilience to social stress is determined by local sleep changes within the prelimbic (PrL) cortex, a region critical for top-down control of stress-responsive circuits. To test this, we conducted longitudinal single-unit and local field potential (LFP) recordings in the PrL cortex of male mice before and after a 5 d social defeat stress paradigm. Our results demonstrate that population-wide neuronal silences, or “OFF-periods,” primarily occur during NREM sleep and strongly correlate with the local slow waves. Notably, resilient mice exhibit significantly higher baseline coupling between OFF-period density and the number of slow waves compared with susceptible animals. Following stress, resilient mice showed a unique reorganization of cortical silence patterns, characterized by an increase in shorter OFF-periods and a more uniform temporal distribution across NREM sleep. Furthermore, social stress was associated with a widespread, stochastic-like redistribution of cortical firing rates that was most pronounced in the resilient phenotype. These findings suggest that behavioral resilience is predicted by the capacity for flexible network redistribution and heightened synchronization during local NREM sleep. Furthermore, this study identifies preexisting, localized sleep-dependent signatures—specifically a stronger coupling between OFF-period density and slow-wave activity—that serve as potential predictors of resilience prior to stress.