From glucosensing neurons to CRH neuroedocrine neurons: Circuits and signals

描述(由申请人提供)： 这份提案描述了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员所需的专业知识。这位候选人于2002年获得博士学位，此后一直在神经科学研究所(NRI)和美国国防部从事博士后研究。南加州大学(USC)生物科学系。NRI由大约70名教职员工组成，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特别的优势，这些科学在突触可塑性和释放机制方面有着强大的研究存在。有许多同事可以对候选人的研究有所裨益。拟议的导师拉里·W·斯旺森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方面的专家，这些技术构成了本培训计划的两个主要目标之一的基础。拟议的共同赞助人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的第二个主要目标的基础。这项拟议的研究侧重于确定大脑中对血糖挑战做出反应的葡萄糖敏感神经元的化学表型，并确定这些区域和室旁下丘脑之间的电路，这有助于有机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感受区释放的信号来调节PVH神经元。 公共卫生相关性：糖尿病患者对低血糖的逆调节反应迟钝，可能在感知/反应低血糖方面存在神经损伤。这项拟议的研究旨在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有助于葡萄糖反调节的下丘脑结构联系在一起。

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.