Project Summary Post-traumatic stress disorder (PTSD) is a devastating psychiatric disorder that afflicts more than 7% of all Americans across their lifespan. PTSD increases the risk for inflammatory cardiovascular diseases, such as hypertension, but the etiology of this increased predilection for hypertension after psychological trauma is unknown. Both PTSD and hypertension characteristically display increases in circulating levels of norepinephrine, as well as alterations in T-lymphocyte-driven inflammation, evidence of autonomic system alterations. T-Lymphocytes are highly reactive to norepinephrine, and we have previously reported that splenic T-Lymphocytes exposed to sympathetic catecholamines, including norepinephrine, from the splenic nerve secrete increased levels of interleukin 6 (IL-6) and interleukin 17A (IL-17A); pro-inflammatory cytokines which have been mechanistically linked to the pathogenesis of hypertension. Furthermore, using an accepted model of PTSD known as repeated social defeat, we have recently shown that denervating the splenic nerve, which receives input from both sympathetic and parasympathetic systems and releases exclusively norepinephrine, decreases splenic norepinephrine levels and concurrently levels of splenic T-Lymphocyte IL-6 and IL-17a. Additionally, these observations and the hypertensive response to angiotensin II (Ang II) in animals undergoing psychological trauma were ablated in mice lacking T-Lymphocytes, demonstrating these immune cells are mechanistic in the sensitization to hypertension after trauma. To this end, I hypothesize that psychological trauma alters autonomic signaling culminating in increased norepinephrine release through the splenic nerve, by either sympathetic or parasympathetic pathways, that drives T-Lymphocyte inflammation causing hypertension sensitization. In Specific Aim 1, I will determine the influence of central sympathetic and parasympathetic signaling on inflammation and hypertension sensitization after psychological trauma using chemogenetic technology to ablate each arm of the autonomic system upstream of the splenic nerve. In Specific Aim 2, I will determine the effects of beta-adrenergic receptors mediating T-lymphocyte inflammation and resulting hypertension sensitization after psychological trauma using genetic knockouts of specific beta- adrenergic receptor signaling on T-lymphocytes. Additionally, with my goal of becoming an academic researcher and educator at the R1 level focusing on autonomic and cardiovascular physiology, this project provides the foundational training in autonomics, physiology, and mental health necessary to develop the transferable skills to achieve my goal.