Sex differences in stress-induced dendritic remodeling

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DESCRIPTION (provided by applicant): Women are twice as likely as men to develop stress-related mental illnesses like major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), but the biological substrates of this discrepancy are unknown. These illnesses are frequently characterized by abnormalities in activity and volume of the medial prefrontal cortex (mPFC) and amygdala, regions known to maintain reciprocal connectivity. Both the mPFC and basal nucleus of the amygdala (BA) undergo morphological changes after stress exposure; interestingly, while the mPFC shows atrophy, the BA is in fact reported to hypertrophy. However, it is not known whether these changes occur in neurons that project between the mPFC and amygdala. The current proposal seeks to explore the morphological changes that occur in the BA-projecting neurons in the mPFC after exposure to both chronic and acute stress. I will further ask what sex differences exist in these changes, and what role, if any, estrogen plays in mediating such differences. To get at the nature of the circuitry involved in these processes, I will ask whether muscimol-induced inactivation of the amygdala during stress can prevent the changes seen in the mPFC. Together these studies will help to define the effects of stress on the mPFC-BA circuit at a cellular level, as well as identify potential sites of sex differences in these effects.