Sex-specific prefrontal-hypothalamic control of behavior and stress responding

Area of Science:

• Neuroscience
• Behavioral Biology
• Physiology

Background:

• Daily life stress exacerbates depression and cardiovascular disease.
• Biological mechanisms linking psychological stress to physiological outcomes remain unclear.
• The ventromedial prefrontal cortex (vmPFC) influences behavior and physiology in a sex-specific manner.

Purpose of the Study:

• To investigate whether ventromedial prefrontal cortex (vmPFC) projections to the posterior hypothalamus (PH) regulate stress responses.
• To determine the sex-specific roles of the vmPFC-PH circuit in behavior and physiological stress.

Main Methods:

• Optogenetic stimulation of the vmPFC-PH circuit in male and female rats.
• Assessment of social and motivational behaviors.
• Measurement of physiological stress responses (sympathetic and neuroendocrine).
• Intersectional genetic approach to knockdown synaptobrevin in vmPFC-PH neurons.

Main Results:

• In males, vmPFC-PH circuit stimulation promoted positive motivational valence and reduced sympathetic stress responses.
• The vmPFC-PH circuit was sufficient and necessary for these effects in males.
• In females, the vmPFC-PH circuit did not influence social or preference behaviors.
• In females, the vmPFC-PH circuit was sufficient and necessary to elevate neuroendocrine stress responses.

Conclusions:

• Cortical regulation of stress reactivity and behavior is partly mediated by projections to the hypothalamus.
• The vmPFC-PH circuit plays a sex-specific role in modulating stress responses.
• These findings reveal a neural circuit basis for sex differences in stress adaptation.