Sexually divergent cortical control of affective-autonomic integration

Depression and cardiovascular disease reduce quality of life and increase mortality risk. These conditions commonly co-occur with sex-based differences in incidence and severity. However, the biological mechanisms linking the disorders are poorly understood. In the current study, we hypothesized that the infralimbic (IL) prefrontal cortex integrates mood-related behaviors with the cardiovascular burden of chronic stress. In a rodent model, we utilized optogenetics during behavior and in vivo physiological monitoring to examine how the IL regulates affect, social motivation, neuroendocrine-autonomic stress reactivity, and the cardiac consequences of chronic stress. Our results indicate that IL glutamate neurons increase socio-motivational behaviors specifically in males. IL activation also reduced endocrine and cardiovascular stress responses in males, while increasing reactivity in females. Moreover, prior IL stimulation protected males from subsequent chronic stress-induced sympatho-vagal imbalance and cardiac hypertrophy. Our findings suggest that cortical regulation of behavior, physiological stress responses, and cardiovascular outcomes fundamentally differ between sexes.