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

用于控制可口食物消耗的伤害感受肽中央杏仁核到后脑回路

基本信息

批准号：
10159256
负责人：
James Andrew Hardaway
金额：
$ 15.16万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-20 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10159256
关键词：
Ablation Alcohols Amygdaloid structure Animal Model Appetite Stimulants Appetitive Behavior Area Axon Bathing Behavior Behavior assessment Behavioral Binge Eating Binge eating disorder Biological Factors Brain Brain region Cannulas Cells Chemicals Cholera Toxin Chronic Clinical Complex Consummatory Behavior Consumption Coupled Cues Data Disease Eating Eating Disorders Electrophysiology (science)Emotional Energy Intake Energy Metabolism Environment Environmental Risk Factor Epidemic Equipment Event FOS gene Fiber Food Food Access Future GTP-Binding Proteins Genetic Genetic Identity Goals Health High Fat Diet Home Human Imaging Techniques Immediate-Early Genes Immunohistochemistry Individual Infusion procedures Intake Lead Leadership Ligands Light Measures Mediating Membrane Potentials Mentors Mentorship Metabolism Molecular Mus National Institute of Environmental Health Sciences Neurons Neuropeptides Neurosciences Neurotransmitters North Carolina Nucleus solitarius ORL1 receptor Obesity Opioid Output Palate Pathway interactions Peptides Pharmaceutical Preparations Pharmacology Phenotype Photometry Population Postdoctoral Fellow Presynaptic Terminals Psychiatry Receptor Signaling Research Research Personnel Research Project Grants Rest Rewards Rodent Role Schedule Severities Signal Pathway Signal Transduction Slice Specificity Structure Testing Time Training Universities Viral Weight Gain Whole-Cell Recordings Wild Type Mouse awake base career career development cohort consumption measures diet-induced obesity experience experimental study feeding food consumption genetic approach health science research hindbrain in vivo inward rectifier potassium channel neural circuit neurobiological mechanism neurochemistry neuroimaging nociceptin novel obesity treatment optogenetics parabrachial nucleus postsynaptic postsynaptic neurons pre-clinical prepronociceptin programs relating to nervous system voltage

项目摘要

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.

项目总结