From glucosensing neurons to CRH neuroedocrine neurons: Circuits and signals

从葡萄糖感受神经元到 CRH 神经内分泌神经元：电路和信号

• 批准号: 7684660
• 负责人: ARSHAD M. KHAN
• 金额: $ 12.26万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-10 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7684660
• 关键词: Adrenergic Agents; Animals; Basic Science; Bathing; Biochemistry; Biological Sciences; Bolus Infusion; Brain; CREB1 gene; CRH gene; California; Catecholamines; Cell Fractionation; Cell Nucleus; Chemicals; Deoxyglucose; Doctor of Philosophy; Environment; Faculty; Genetic Transcription; Glucagon; Glucocorticoids; Glucose; Glutamate Receptor; Glutamates; Hypoglycemia; Hypothalamic structure; Image; Immunofluorescence Immunologic; Impairment; In Vitro; Injection of therapeutic agent; Insulin; Label; Learning; Measures; Mediating; Memory; Mentors; Mitogen-Activated Protein Kinases; Molecular; Neuroanatomy; Neurons; Neurosciences; Neurosciences Research; Neurosecretory Systems; Neurotransmitters; Organism; Pathway interactions; Pattern; Peptides; Phenotype; Phosphotransferases; Population; Postdoctoral Fellow; Preparation; Protein Biochemistry; Regulation; Research; Research Institute; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Signal Transduction; Slice; Source; Staining method; Stains; Structure of nucleus infundibularis hypothalami; Synaptic plasticity; System; Techniques; Testing; Thick; Time; Tracer; Training; Training Programs; Universities; Vision; adrenergic; authority; base; brain tissue; cell type; computational neuroscience; counterregulation; design; diabetic; extracellular; gamma-Aminobutyric Acid; hindbrain; in vivo; melanocyte; neurochemistry; neurotransmitter release; noradrenergic; public health relevance; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): This proposal, which describes a 3-4 year training program, is designed to provide the candidate with the opportunity of solving an important basic research question while simultaneously acquiring the expertise needed to become a full-time independent investigator in an academic environment. The candidate received his Ph.D. in 2002 and has since been conducting research as a postdoctoral fellow at the Neurosciences Research Institute (NRI) and the Dept. of Biological Sciences at the University of Southern California (USC). The NRI consists of about 70 faculty, of whom approximately half are located in the Hedco Neuroscience Building or in close vicinity on the main USC campus. The NRI has particular strengths in computational neuroscience, systems neuroscience (learning and memory, motivational systems, vision), and cellular and molecular neuroscience where there is a strong research presence in synaptic plasticity and release mechanisms. There are many colleagues who can be of benefit to the candidate's research. The proposed mentor, Dr. Larry W. Swanson, is an acknowledged world-class authority on neuroanatomy and an expert on the neuroanatomical tract tracing techniques which form the basis of one of two major Aims of this training proposal. The proposed co-sponsor, Dr. Michel Baudry, is similarly an acknowledged authority on neurochemistry, and an expert at cellular and molecular biochemistry related to in vitro slice preparations of brain tissue, which forms the basis of the second major Aim of this training proposal. The proposed research focuses on defining the chemical phenotypes of glucosensing neurons in the brain that respond to glycemic challenges and to define the circuits between these regions and the paraventricular hypothalamus, which helps the organism respond to these challenges by initiating glucocorticoid responses. Additionally, the plan also focuses on the regulation of PVH neurons by signals that are released by these glucosensing regions. PUBLIC HEALTH RELEVANCE: Diabetics suffering from blunted counterregulatory responses to hypoglycemia may have neural impairments in sensing/responding to hypoglycemia. The proposed research aims to define what the normal brain activation pattern to hypoglycemia is, and how neurons sensing this are connected to hypothalamic structures that contribute to glucose counterregulation.

描述（由申请人提供）： 该提案描述了一个3-4年的培训计划，旨在为候选人提供解决重要基础研究问题的机会，同时获得成为学术环境中全职独立调查员所需的专业知识。候选人获得了博士学位。在2002年，并一直在进行研究，作为博士后研究员在神经科学研究所（NRI）和系。南加州大学（USC）生物科学系。NRI由大约70名教师组成，其中大约一半位于Hedco Neuroscience Building或USC主校区附近。NRI在计算神经科学，系统神经科学（学习和记忆，动机系统，视觉）以及细胞和分子神经科学方面具有特别的优势，其中在突触可塑性和释放机制方面有很强的研究。有许多同事可以对候选人的研究有所帮助。导师Larry W. Swanson是公认的世界级神经解剖学权威，也是神经解剖学追踪技术的专家，该技术构成了本培训计划的两个主要目标之一。拟议的共同发起人Michel Baudry博士同样是公认的神经化学权威，也是与脑组织体外切片制备相关的细胞和分子生物化学方面的专家，这构成了本培训提案的第二个主要目标的基础。拟议的研究重点是定义大脑中响应血糖挑战的葡萄糖传感神经元的化学表型，并定义这些区域和室旁下丘脑之间的回路，这有助于生物体通过启动糖皮质激素反应来应对这些挑战。此外，该计划还侧重于通过这些葡萄糖敏感区域释放的信号来调节PVH神经元。 公共卫生相关性：患有对低血糖的迟钝的反调节反应的糖尿病患者可能在感知/响应低血糖方面具有神经损伤。这项研究的目的是确定低血糖的正常大脑激活模式是什么，以及感觉到这一点的神经元如何与下丘脑结构连接，从而促进葡萄糖反调节。