Fear and anxiety disorders are the most common subtype of neuropsychiatric diseases in the United States with a lifetime prevalence of 30% (Ferrara et al., 2021). Specifically, posttraumatic stress disorder (PTSD) can be examined scientifically as an anxiety disorder that affects over 8% of the population (Miles & Maren, 2019; Almli et al., 2014). PTSD is unique among neuropsychiatric disorders due to the fact that the initiating factor can usually be identified, and it can be thought of as the dysregulation of fear and stress. Current research aims to develop an increased understanding of the neural circuits underlying these pathways, as currently these mechanisms are widely unknown (Almli et al., 2014). 

Previous studies have linked early life stress (ELS) to increased susceptibility to development of emotional and cognitive disorders later in life, one of which being our focus of study, PTSD. In our experiment, we will use a rat model and inflict early life stress by performing a repeated foot shock method. This ELS will facilitate Stress Enhanced Fear Learning (SEFL) in the animals to serve as a reliable and robust preclinical model of PTSD and prompts a long-lasting sensitization of fear conditioning (Quinn et al., 2014; Rau et al., 2005; Rau & Fanselow, 2009). Using both freezing analysis and western blotting, this combines a behavioral approach and a molecular approach to evaluate the effect of PTSD on specific brain regions. 

The two brain regions we will be examining are the bed nucleus of the stria terminalis (BNST) and the dorsal raphae nucleus (DRN). The BNST has been identified as having a critical role in stress-related behavior processing, as it is interconnected with other emotional processing regions such as the prefrontal cortex, amygdala, and hippocampus (Ferrara et al., 2021). Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter that plays an important role in regulating emotion. The BNST receives 5-HT body projections from the DRN when the DRN is highly activated. Neurons within the DRN become activated upon interacting with corticotropin releasing hormone (CRH) while experiencing an uncontrollable stressor (Hammack et al., 2002). 

This experiment aims to increase understanding of how serotonergic pathways are affected by ELS and determine whether the BNST and DRN play a role in the development of PTSD-like behavior. In addition to learning laboratory skills and specific procedures, we will also improve as scientists through use of the scientific method, interpretation of results, and communication of findings at the Miami University Undergraduate Research Forum this Spring. 

Keywords: PTSD, Bed Nucleus of the Stria Terminalis (BNST), Dorsal Raphae Nucleus (DRN), Early Life Stress (ELS), Stress Enhanced Fear Learning (SEFL)

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Xiang, M., Jiang, Y., Hu, Z., Yang, Y., Du, X., Botchway, B. O., Fang, M. (2019). Serotonin receptors 2A and 1A modulate anxiety-like behavior in post-traumatic stress disordered mice. American Journal of Translational Research, 11(4), 2388-2303.