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， 药理学系饮食失调卓越中心， 查佩尔山的北卡罗来纳州大学精神病学。 职业目标：我的最终目标是了解调节可口食物摄入的神经回路 导致肥胖症和暴食症等疾病。通过研究潜在的 在这些神经化学定义的神经元集合中，我将 开发针对肥胖和暴食症的靶向、新型临床前治疗方法， 构建有效的肥胖和暴食症动物模型。 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 获得额外的指导培训1）电路神经科学，包括测光，高级 光遗传学、化学遗传学和电生理学; 2）小鼠操作行为;和3）临床 肥胖表型和代谢在目前的建议。 研究项目：该项目利用初步数据，显示了 在中央杏仁核中表达前原啡肽的神经元（PCA 1CeA神经元）：促进 可口的食物摄入，调节饮食引起的肥胖的严重程度，并通过以下方式促进奖励： 臂旁核（PBN）和孤束核（NTS）的传入。我的目标是（1） 用免疫组织化学方法检测PGEA神经元在操作性适口性食物摄取过程中的动态活动状态， 体内纤维光度法，2）确定PBN和NTS中的伤害感受素信号传导对神经元的作用 活性和该途径在操作性适口食物摄入中的必要作用，以及3）使用途径- 特异性抑制性光遗传学和化学遗传学，以探测PGEX CeA通路的特异性作用 在操作性可口食物摄入期间，PBN和NTS。在未来的独立应用（R 01）中，我 将评估长期食用可口食物后，PAPOCEA网络的回路和分子可塑性 和饮食引起的肥胖。 环境：研究将主要在查佩尔山的北卡罗来纳州大学进行 国家环境健康科学研究所进行的一些实验 在北卡罗来纳州达勒姆的研究三角公园进行的一项研究计划。 导师：核心导师团队由首席导师托马斯卡什博士组成，他是一位 回路神经科学和完善行为的研究员，以及共同负责人辛西娅·布利克博士 导师，他是全国著名的肥胖和饮食失调研究专家。卡莉·诺斯博士a 共同导师，是临床肥胖表型和遗传学的主要研究人员。Joyce Besheer博士a 共同导师，是一个非常有经验的研究人员在啮齿动物的操作行为。崔国宏博士及李博士。 顾问迈克尔·克拉舍斯（Michael Krashes）拥有用于体内纤维光度测定的设备，并定期使用， 基因编码的Ca 2+指标在清醒，自由行为的小鼠。托德蒂尔博士，一名顾问，是 神经肽信号和小鼠行为中的局部药理学操作方面的专家。 他们将一起提供专业知识来完成科学目标，指导我完成 我的训练和领导能力，以促进我成为一名独立调查员的过渡。