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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：
10413010
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/10413010
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 antagonist 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.

项目摘要候选人：我是鲍尔斯酒精研究中心的博士后研究助理以及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）神经电路，包括测光，先进的光遗传学，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。