http://hdl.handle.net/2374.MIA/5158 2026-04-08T06:58:44Z http://hdl.handle.net/2374.MIA/7051 Social buffering of acute early life stress sex-dependently ameliorates fear incubation in adulthood Reichert, Amanda; Riddle, Collin; Quinn, Jennifer Social buffering may reduce the persistent impacts of acute early life stress (aELS) and, thus, has important implications for anxiety- and trauma-related disorders. First, we assessed whether aELS would induce maladaptive fear incubation in adult mice, a PTSD-like phenotype. Overall, animals showed incubation of fear memory in adulthood independent of aELS condition. Next, we investigated whether social interaction with the dam and/or the littermates following the aELS session would eliminate adult fear incubation. Males demonstrated social buffering only if the dam was present, and females demonstrated social buffering only if the littermates were present. Finally, we assessed whether social buffering following aELS exposure reduces consolidation of the associative fear learning that occurs during the aELS session. Animals received aELS followed by isolation or social interaction (dam + littermates). Over the next four consecutive days, they received 30-minute exposures to the context (test/extinction). There were no differences between isolation and social interaction on contextual fear memory expression or its extinction. Taken together, these results indicate that social buffering reduces the impact of non-associative processes during aELS on subsequent adult fear memory in a sex-dependent manner, and further supports social buffering as an important intervention following early trauma experiences. http://hdl.handle.net/2374.MIA/7005 5-HT2C receptors in the BNST modulate contextual fear conditioning without affecting acute ELS-enhanced fear learning in adult rats Minshall, Brianna; Wasylyshyn, Catherine; Brand, Kate; Bartoszek, Caroline; Seipel, Kennedy; Booms, Madeline; Chappell, Lucy; Reichert, Amanda; Dowell, Jacob; Buck, Angeles; Beckett, Henry; Lowry, Christopher; Quinn, Jennifer Abstract: Background/Objectives: Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with women having increased vulnerability for diagnosis; however, the mechanisms of this increased vulnerability remain unknown. PTSD involves a complex network of highly interconnected brain regions, including the bed nucleus of the stria terminalis (BNST). The precise circumstances that engage the BNST and the neural mechanisms that mediate its involvement in PTSD are not fully known. Serotonin (5-HT) release into the BNST yields increased expression of both fear and anxiety, specifically through 5-HT2C receptor signaling. Methods: Here, we investigated whether BNST 5-HT2C receptor signaling is necessary for the stress-enhancement of adult contextual fear learning that is observed in animals previously exposed to acute early life stress. Rats received 0 or 15 footshocks on postnatal day 17, an established model of stress-enhanced fear learning (i.e., SEFL). In adulthood, rats received bilateral infusions of vehicle, a 5-HT2C receptor antagonist (RS-102221), or a 5-HT2C receptor agonist (MK-212) into the BNST 15 minutes prior to 1-footshock contextual fear conditioning in a novel context. The next day, rats were returned to the fear conditioning context to assess their fear memory (freezing). Results: BNST infusions of RS-102221 reduced contextual fear conditioning, independent of aELS condition and sex. Infusions of MK-212 had no effect. Conclusions: Taken together, these data suggest that serotonergic signaling through 5-HT2C receptors in the BNST contribute to contextual fear conditioning, but not SEFL. http://hdl.handle.net/2374.MIA/6997 Acute early life stress alters threat processing in adult rats Minshall, Brianna L.; Peguero, Allison Z.; Scheive, Katelyn M.; Wasylyshyn, Catherine F.; Claflin, Dragana I.; Quinn, Jennifer J. Individuals diagnosed with stress-related psychiatric disorders in adulthood are likely to have experienced early life stress, suggesting that early adversity is an important vulnerability factor in subsequent development of trauma- and anxiety-related psychiatric illness. It is important to develop animal models of psychiatric dysfunction to determine evident vulnerability considerations, potential biomarkers, and novel treatment avenues to improve the human condition. In our model of acute early life stress (aELS), 15 footshocks are delivered in a single session on postnatal day (PND) 17. The following experiments investigated the persistent impacts of our aELS procedure on stress-enhanced fear learning, anxiety-related behaviors, maintenance of fear, and resistance to extinction in adult male and female rats. The findings from these experiments demonstrate that our aELS procedure yields enhanced fear learning and increased anxiety. This enhanced fear is maintained over time, yet it extinguishes normally. Taken together, these results demonstrate that exposure to 15-footshocks during a single session early in life (PND 17) recapitulates a number of important features of trauma- and anxiety-related disorder symptomatology, but not others. Future studies are needed to determine the persistent physiological phenotypes resulting from aELS, and the neurobiological mechanisms that mediate these long-term changes. http://hdl.handle.net/2374.MIA/6996 Sex differences in acute early life stress-enhanced fear learning in adult rats Minshall, Brianna; Skipper, Rachel; Riddle, Collin; Wasylyshyn, Catherine; Claflin, Dragana; Quinn, Jennifer Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress-enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.