A Nociceptin Central Amygdala to Hindbrain Circuit for the Control of Palatable Food Consumption

Project Summary
Candidate: I am a Postdoctoral Research Associate within the Bowles Center for Alcohol Studies
and the UNC Center of Excellence for Eating Disorders in the Departments of Pharmacology and
Psychiatry at the University of North Carolina at Chapel Hill.
Career Goals: My ultimate goal is to understand the neural circuits that regulate palatable food intake
that contribute to diseases like obesity and binge eating disorder. By researching the underlying
signaling pathways and molecular circuitry in these neurochemically defined neuron ensembles, I will
develop targeted, novel preclinical treatments for obesity and binge eating disorder for testing in
construct valid animal models of obesity and binge eating disorder.
Career Development: My current expertise is in molecular neuroscience and genetics, so I hope to
gain additional mentored training in 1) neural circuits including photometry, advanced optogenetics,
chemogenetics, and electrophysiology; 2) mouse operant behavior; and 3) clinical obesity
phenotypes and metabolism within the current proposal.
Research Project: This project leverages preliminary data that shows a specific role for
prepronociceptin-expressing neurons in the central amygdala (PnocCeA neurons) in: promoting
palatable food intake, modulating the severity of diet-induced obesity, and promoting reward through
its inputs to the parabrachial nucleus (PBN) and nucleus of the solitary tract (NTS). I aim to 1)
measure the dynamic activity state of PnocCeA neurons during operant palatable food intake using in
vivo fiber photometry, 2) determine the role of nociceptin signaling in the PBN and NTS on neural
activity and the requisite role of this pathway in operant palatable food intake, and 3) use pathway-
specific inhibitory optogenetics and chemogenetics to probe the specific role of the PnocCeA pathway
to the PBN and NTS during operant palatable food intake. In future independent applications (R01s), I
will assess circuit and molecular plasticity of PnocCeA networks following chronic palatable food
access and diet-induced obesity.
Environment: Research will be primarily performed at the University of North Carolina at Chapel Hill
with some experiments performed at the National Institute of Environmental Health Sciences
research program at Research Triangle Park in Durham, NC.
Mentorship: The core mentorship team consists of Dr. Thomas Kash, lead mentor, who is a leading
researcher in circuit neuroscience and consummatory behavior, and Dr. Cynthia Bulik, co-lead
mentor, who is a nationally renowned expert in obesity and eating disorder research. Dr. Kari North, a
co-mentor, is a leading researcher in clinical obesity phenotyping and genetics. Dr. Joyce Besheer, a
co-mentor, is a very experienced researcher in rodent operant behavior. Dr. Guohong Cui and Dr.
Michael Krashes, both consultants, have equipment for and routinely use in vivo fiber photometry of
genetically encoded Ca2+ indicators in awake, freely-behaving mice. Dr. Todd Thiele, a consultant, is
an expert in neuropeptide signaling and local pharmacological manipulations during mouse behavior.
Together, they will provide expertise to accomplish the scientific aims, mentorship for me to complete
my training, and leadership to promote my transition to being an independent investigator.