Sex differences in innate and adaptive neural oscillatory patterns predict resilience and susceptibility to chronic stress in rats

Abstract

Major Depressive Disorder (MDD) is a chronic illness with higher incidence in women. Dysregulated neural oscillatory activity is an emerging mechanism underlying MDD, however whether sex differences in these rhythms contribute to the development of MDD symptoms is unknown. Using the chronic unpredictable stress model, we found that stress-resilient and susceptible animals exhibited sex-specific oscillatory markers in the prefrontal cortex, cingulate cortex, nucleus accumbens and hippocampus. Resilient females were predominantly characterized by increased hippocampal theta power and coherence, while resilient males exhibited increased system-wide gamma coherence. In susceptible animals, the females displayed a widespread increase in delta and reduced theta power, however males showed few within-sex differences that could delineate stress susceptibility from resilience. Finally, stress responses were mediated by the temporal recruitment of specific neural pathways, culminating in system-wide changes that correlated with the expression of depression-like behaviours. These findings show that neurophysiological responses can serve as predictive markers of behaviours linked to depression in a sex-specific manner.