PROJECT SUMMARY Lack of appetite is a common symptom of acute and chronic inflammatory diseases. While this response is likely adaptive in acute illness, in chronic diseases it may result in malnutrition leading to morbidity and mortality. Inflammation-induced anorexia is mediated primarily by immune cell-secreted inflammatory cytokines. One of the most potent and well-studied anorexigenic cytokines is interleukin-1β (IL-1β). Despite prolific literature on this compound, the mechanism by which it signals to the brain to generate the psychological and behavioral state of anorexia is incompletely understood. We have obtained preliminary data demonstrating that IL-1β influences the dynamics of canonical “hunger” neurons in the arcuate nucleus of the hypothalamus. Our current proposal seeks to expand upon these initial observations by determining how peripherally administered IL-1β modulates the activity of deep brain nuclei to suppress food intake, focusing on contributions from peripheral sensory neurons, especially vagal afferent populations. To accomplish this, we will use a suite of cutting-edge tools including calcium imaging with fiber photometry, chemogenetic and behavioral approaches, and microsurgical techniques. Our experiments will address how IL-1β promotes anorexia at the circuit level with the ultimate goal of revealing novel circuit-based therapeutic approaches to treat the nutritional complications of inflammatory disease. In addition to completing the proposed experiments, this project will enable me to obtain formal training in both scientific and professional areas. I will solidify my lab-based knowledge in computer programming and immunology by attending workshops and taking courses in these areas. I will pursue microsurgical training that will enable me to perform the complex surgeries required for this project. Finally, I will gain valuable formal training in professional skills including mentorship and grantsmanship through workshops and programs offered through the university. Taken together, completing the work outlined in this proposal will leave me ideally positioned to obtain a postdoctoral fellowship in a top lab and ultimately a faculty position where my lab will work at the intersection of neuroimmunology, metabolism and homeostasis.