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-1ß and TNF-a
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.