Sex Specific Neuroanatomical Markers Of Vulnerability In Animal Model Of PTSD

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DESCRIPTION (provided by applicant): A majority of Americans will be exposed to a trauma in their lifetimes, but only 10% of those people will develop Post-Traumatic Stress Disorder (PTSD) as a result. Women, however, are twice as likely as men to develop PTSD after a trauma. Identification of the neurobiological factors that contribute to PTSD susceptibility and resilience in women is critical to developing more effective treatments, but basic science research into this problem is generally lacking. PTSD is characterized by a strong association between the trauma and its associated cues, a behavioral phenotype that may be the result of disrupted connectivity between the medial prefrontal cortex (mPFC) and amygdala. This pathway has been shown in animal models to mediate extinction from conditioned fear, and animals that fail to extinguish may be a good model of PTSD vulnerability. This proposal will explore neuroanatomical markers of vulnerability and resilience in male and female rats. Animals will be behaviorally characterized in classic cued fear conditioning and extinction protocols, identifying sex differences in variability in these behavioral tests. Using a combinatio of retrograde tracer and iontophoretic fluorescent microinjections, the dendritic morphology of mPFC neurons that project to the amygdala will be analyzed in animals that show high (vulnerable) and low (resilient) levels of freezing after extinction. These experiments will establish baseline sex differences in variability in fear behavior, which will be useful for interpreting future sex differences studies. Moreover, morphology analysis will provide a comprehensive neuroanatomical profile of vulnerability and resilience in both males and females, thus identifying areas that signify vulnerability uniquely in females. PUBLIC HEALTH RELEVANCE: Post-Traumatic Stress Disorder (PTSD) afflicts only 10% of people exposed to a trauma, but occurs twice as frequently in women as in men. Alterations in the structure and function of neurons that project from the medial prefrontal cortex (mPFC) to the amygdala may underlie the symptoms of PTSD, but sex differences in this pathway have not been thoroughly explored. This project will morphologically characterize neurons in the mPFC-amygdala pathway in male and female rats and correlate these measures with behavior in a model of PTSD, thus identifying sex-specific neuroanatomical markers of vulnerability and resilience.