Every year more than 15,000 – 30,000 Veterans and service members suffer a traumatic brain injury (TBI) according to the Department of Defense (DOD). Mortality from TBI is high and many survivors suffer from reduced life expectancy and persistent disability, including post-traumatic stress disorder (PTSD), which might be due to autonomic nervous system (ANS) dysfunction. ANS dysfunction can be quantified by reduced heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS), which are associated with poor neurological outcomes, arrhythmias, and death. The proposed studies will assess TBI-impaired central neuronal circuitry to address the overall hypothesis that TBI-induced dysautonomia is not only a prognostic biomarker, but also a pathogenic element compromising Veteran's health. This proposal investigates the amygdala, a brain region that is related to fear, anxiety and PTSD, as well as in behavioral pathology following TBI, but is under-studied in the ANS dysfunction following TBI. The amygdala is of interest because it: 1) controls ANS responses in humans and rodents; 2); is damaged in human TBI and animal models; and 3) contributes to fear and anxiety in humans and rodents. This constellation of factors is critical for Veterans health. A novel, rotational TBI model, that is bioengineered to mimic human injury will be employed in male and female rats. This TBI model induces behavioral and ANS deficits, and damages the amygdala. The proposed studies will implement a multi-faceted approach to examine cardiovascular (CV) disturbances following TBI by monitoring blood pressure (BP) via surgically implanted radiotelemetry units from which heart rate (HR) , HRV, and BRS will be derived in awake freely moving male and female rats during: 1) inactive, resting states; 2) pharmacological stressors that disturb CV homeostasis; 3) pharmacological and chemogenetic manipulation of the amygdala; and 4) fear conditioning with correlation between amygdala-dependent behaviors and CV parameters. Aim 1 will examine the role of the amygdala in dysautonomia after TBI using HRV and BRS in response to pharmacological stressors (systemic phenylephrine and nitroprusside) and amygdala microinjections. The basolateral (BLA) and central amygdala (CeA) will be targeted with gamma-aminobutyric acid (GABA) agonists or antagonists because GABAergic neurons control amygdala outflow to behavioral circuits and CV centers. Aim 2 will assess chemogenetic manipulation of amygdala circuits on CV control. Excitatory or inhibitory DREADDs (designer receptors exclusively activated by designer drugs) will be expressed in the amygdala. HRV and BRS will be evaluated at rest and following BP changes due to pharmacological stressors with DREADD ligand or vehicle to confirm amygdala neurons as a potential therapeutic target for ANS dysfunction after TBI. Aim 3 will quantify the relationship between amygdala mediated fear behaviors and ANS parameters following TBI. Behaviors d...