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: 7803474
• 负责人: ARSHAD M. KHAN
• 金额: $ 0.11万
• 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/7803474
• 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）： 该提案描述了一个为期 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，同时获得在学术环境中成为全职独立研究者所需的专业知识。该候选人获得了博士学位。 2002 年获得博士学位，此后一直在神经科学研究所 (NRI) 和南加州大学 (USC) 生物科学系进行博士后研究。 NRI 由约 70 名教职人员组成，其中大约一半位于 Hedco 神经科学大楼或南加州大学主校区附近。 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独特的优势，其中在突触可塑性和释放机制方面拥有强大的研究实力。有很多同事可以对候选人的研究有所帮助。拟议的导师 Larry W. Swanson 博士是公认的世界级神经解剖学权威，也是神经解剖束追踪技术的专家，该技术构成了本培训提案的两个主要目标之一的基础。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专家，这构成了本培训提案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，该计划还关注通过这些葡萄糖传感区域释放的信号对 PVH 神经元的调节。 公众健康相关性：对低血糖的反调节反应迟钝的糖尿病患者可能在感知/反应低血糖方面存在神经损伤。拟议的研究旨在定义低血糖的正常大脑激活模式是什么，以及感知这种模式的神经元如何与有助于葡萄糖反调节的下丘脑结构相连接。