Determining CGRP neuron contribution to inflammation-induced anorexia - PROJECT SUMMARY The brain maintains energy homeostasis by integrating peripheral signals to balance food intake with energy expenditure. This can be perturbed in chronic inflammatory states such as inflammatory bowel disease (IBD), resulting in anorexia. The clinical phenomenon of inflammation-associated anorexia is well-established, and inflammatory cytokines such as IL-1β and TNF-α that are elevated in patients with active IBD have been known cause anorexia in laboratory settings for decades. However, the neural circuit-based mechanisms underlying this phenomenon remain poorly understood. This represents a crucial knowledge gap, as targeted therapies for inflammation-related anorexia and malnutrition are lacking. Parabrachial CGRP neurons represent a well- defined anorexic node, decreasing food intake in response to gastrointestinal satiety signals, aversive stimuli, and cancer progression. Here, I will determine CGRP neuron contribution to IBD-associated anorexia. In proposal, neural the this will use cutting edge echniques including in vivo calcium imaging, genetically driven modulation of activity, and microsurgical approaches combined with a well-established mouse model of IBD to dissect role of this critical neural population in inflammation-induced anorexia. I t Taken together, this proposal will test my hypothesis that IBD-associated anorexia is mediated at least partially through CGRP neurons as an initial step to dissecting the neuronal circuitry underlying inflammation-induced anorexia more broadly. The results of these experiments will reveal in unprecedented detail how inflammatory signals may impact hunger circuitry in IBD to promote anorexia. In addition to pursuing this innovative project, this proposal seeks to advance my professional training. Specifically, I will acquire skills in calcium imaging and computer programming, engage in formal coursework in immunology and biostatistics, and seek formal training in professional realms including grantsmanship and leadership. Taken together, the successful completion of this proposal will prepare me for a career as an independent academic neurologist and scientist with a research focus on how the brain maintains homeostasis in health and how this can be disrupted in disease.
