Increased activity of the sympathetic nervous system is a hallmark in the development of heart failure (HF). The role of central inflammation as a driver of sympathetic overactivity and neurohumoral activation in HF has been increasingly appreciated, and TNF-α in particular has been identified as having a major role. However, clinical use of therapeutic agents targeting TNF-α is contraindicated during heart failure, suggesting a more complex mechanism underlying TNF-α action in this context. Recent work has shown that TNF receptors 1 and 2 (TNFR1 &TNFR2, respectively) play opposing roles on cardiomyocytes, with TNFR1 mediating the pathological effects of TNF-α following myocardial infarction and TNFR2 playing a protective role. However, the functions of these receptors within the central nervous system and specifically with respect to the effects of TNF-α on sympathoexcitation is not fully clear. Thus, the goal of this research is to determine the role of TNFR1/TNFR2 in the PVN in TNF-α-induced sympathic excitation in normal and HF rats, and to determine whether chronic inhibition of TNFR1 and/or activation of TNFR2 in the brain has a beneficial effect on sympathetic regulation and ventricular function in HF.