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 北卡罗来纳大学进食障碍卓越中心药理学和 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美味食物摄入量的神经回路 这会导致肥胖和暴饮暴食等疾病。通过研究潜在的 在这些神经化学定义的神经元集合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有针对性的新临床前治疗方法，用于在 构建有效的肥胖和暴食障碍动物模型。 职业发展：我目前的专长是分子神经科学和遗传学，所以我希望 获得1)电路神经科学方面的额外指导培训，包括光度学、高级 光遗传学、化学遗传学和电生理学；2)小鼠的操作行为；3)临床 肥胖症的表型和代谢在当前的建议中。 研究项目：该项目利用了初步数据，这些数据表明 中央杏仁核中表达前胶原的神经元(PnocCeA神经元)促进 可口的食物摄入量，调节饮食诱导的肥胖的严重程度，并通过 投射至臂旁核和孤束核。我的目标是1) 使用In测量可口食物摄入过程中PnocCeA神经元的动态活动状态 活体纤维光度法，2)确定伤害素信号在PBN和NTS对神经的作用 这一途径的活性及其在可口食物摄取中的必要作用，以及3)使用途径-- 特异性抑制光遗传学和化学遗传学研究PnocCeA通路的特殊作用 在手术的可口食物摄入过程中向PBN和NTS转移。在未来的独立应用(R01s)中，我 将评估慢性美味食物后PnocCeA网络的回路和分子可塑性 获取和饮食诱导的肥胖。 环境：研究将主要在北卡罗来纳大学教堂山分校进行 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研究三角公园的研究计划。 导师关系：核心导师团队由首席导师Thomas Kash博士组成，他是一位 电路神经科学和消费行为的研究人员，Cynthia Bulik博士，共同领导 他是全国著名的肥胖和进食障碍研究专家。卡里·诺斯博士，一位 共同导师，是临床肥胖表型和遗传学的领先研究人员。乔伊斯·贝希尔博士，一位 共同导师，是一位在啮齿动物操作行为方面非常有经验的研究人员。崔国宏博士和崔国宏博士 迈克尔·克拉什，两位顾问，都有设备，并经常使用体内纤维光度测量 清醒的、行为自由的小鼠的基因编码的钙指示物。托德·蒂勒博士是一名顾问， 在老鼠行为过程中神经肽信号和局部药物操作方面的专家。 在一起，他们将提供专业知识来实现科学目标，指导我完成 我的培训和领导力，以促进我向独立调查员的转变。