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

• 批准号: 10103903
• 负责人: James Andrew Hardaway
• 金额: $ 8.48万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 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/10103903
• 关键词: Nociceptin; Central; Amygdala; Hindbrain; Circuit

Project Summary Candidate: I am an NIH T32 Postdoctoral Fellow 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) circuit neuroscience 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.

项目摘要 候选人：我是鲍尔斯酒精研究中心的NIH T32博士后研究员 UNC在药理学部门和 北卡罗来纳大学教堂山分校的精神病学。 职业目标：我的最终目标是了解调节可口食品摄入的神经回路 这有助于肥胖和暴饮暴食等疾病。通过研究基础 这些神经化定义的神经元合奏中的信号通路和分子电路，我将 开发针对肥胖和暴饮暴食障碍的针对性的新型临床前治疗，以进行测试 构建有效的肥胖和暴饮暴食障碍动物模型。 职业发展：我目前的专业知识是分子神经科学和遗传学，所以我希望 在1）电路神经科学中获得额外的指导训练，包括光度法，高级 光遗传学，化学遗传学和电生理学； 2）鼠标操作行为； 3）临床 当前提案中的肥胖表型和代谢。 研究项目：该项目利用初步数据，显示了特定作用 中央杏仁核（PNOCCEA神经元）中表达前摄影的神经元：促进 可口的食物摄入量，调节饮食引起的肥胖症的严重程度，并通过 它输入了孤立的核核（PBN）和核的核（NTS）。我的目标是1） 在操作可口的食物摄入过程中测量PNOCCEA神经元的动态活性状态 体内纤维光度法，2）确定Nocieptin信号在PBN和NTS中的作用 活动和该途径在可口的食物摄入量中的必要作用，3）使用途径 - 特定的抑制性光遗传学和化学遗传学，以探测PNOCCEA途径的特定作用 在操作剂可口的食物摄入量期间，PBN和NTS。在将来的独立应用程序（R01）中，我 将评估慢性可口食品后PNOCCEA网络的电路和分子可塑性 进入和饮食引起的肥胖症。 环境：研究将主要在北卡罗来纳大学教堂山的分校进行 在国家环境健康科学研究所进行的一些实验 北卡罗来纳州达勒姆市研究三角公园的研究计划。 指导：核心指导团队由首席导师托马斯·卡什（Thomas Kash）博士组成，他是领导者 电路神经科学和完善行为的研究人员，以及辛西娅·布里克（Cynthia Bulik）博士，共同领导 导师是一位在肥胖和饮食失调研究领域的全国知名专家。 Kari North博士，A 同事是临床肥胖表型和遗传学的领先研究人员。 Joyce Besheer博士，一个 Co-Incermor是一位经验丰富的啮齿动物操作行为研究人员。 Guohong Cui博士和博士 两位顾问迈克尔·克拉什斯（Michael Krashes）都有用于体内纤维光度法的设备 在清醒的，自由地行为的小鼠中遗传编码的Ca2+指标。顾问Todd Thiele博士是 在小鼠行为过程中，神经肽信号传导和局部药理操作的专家。 他们将共同提供专业知识来完成科学目标，并为我完成指导 我的培训和领导才能促进我过渡到独立调查员。