Transmission Electron Microscopy Service for SPARC Consortium Investigators

为 SPARC 联盟研究人员提供的透射电子显微镜服务

• 批准号: 10008152
• 负责人: LEIF A HAVTON
• 金额: $ 6.35万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2019-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10008152
• 关键词: Address; Anatomy; Animal Model; Area; Australia; Autonomic ganglion; Axon; Back; Biological; Collaborations; Custom; Data; Data Collection; Development; Device Designs; Doctor of Philosophy; Endocrine; Family suidae; Ferrets; Florida; Funding; Ganglia; Goals; Heart; Horns; Human; Hypoglossal nerve structure; Image; Immunoelectron Microscopy; Investigation; Knowledge; Laboratories; Lower urinary tract; Mammals; Modeling; Mus; Myelinated nerve fiber; Nerve; Nerve Tissue; Nervous system structure; Neurosecretory Systems; Organ; Oryctolagus cuniculus; Pancreas; Pelvis; Peripheral; Peripheral Nerves; Plant Resins; Process; Protocols documentation; Rattus; Regulation; Research; Research Personnel; Respiration; Respiratory System; Rodent; Services; Side; Spinal Cord; Structure; Study models; Synapses; Synaptic Potentials; Thinness; Tissue Embedding; Tissue Harvesting; Tissue Preservation; Tissues; Translations; Transmission Electron Microscopy; Universities; Visceral; Work; autonomic nerve; blood glucose regulation; connectome; data resource; functional outcomes; gastrointestinal system; gut-brain axis; human tissue; improved; member; model design; myelination; nerve supply; neural circuit; neuroregulation; relating to nervous system; sex; tissue processing

PROJECT SUMMARY/ABSTRACT Organ function may be modulated by stimulating peripheral activity and targeting, for instance, peripheral nerves and autonomic ganglia. However, the detailed functional and anatomical organization is not well understood for autonomic nerves, ganglia and organs involved with visceral functions. Significant knowledge gaps exist with regards to the neural control of many organ functions, including those of the heart, respiratory system, lower urinary tract, and gastro-intestinal system. An improved understanding of the various components of neural circuitries and innervation of peripheral organs is needed in order to provide improved modeling and design of devices to allow for optimal modulation of select organ functions. Transmission electron microscopy (TEM) allows for the identification of the fine structure of neural tissues to characterize, for instance, axonal composition and myelination, organization of neural circuitry in autonomic ganglia, and innervation of autonomic targets. The proposed studies will aim at establishing a TEM service for investigators supported by the Stimulating Peripheral Activity to Relieve Conditions (SPARC) consortium. A total of 6 SPARC-funded projects, which include 7 SPARC-affiliated investigator laboratories, with defined needs for TEM studies have been identified. The projects include studies on the autonomic control of the heart, brain-gut interactions, hypoglossal nerve-influences on respiration, lower urinary tract function, neuro-endocrine regulation of glucose, and modeling of vagal nerve functions. TEM studies will include detailed characterization of myelinated and unmyelinated axons in visceral and somatic nerves as well as organization of autonomic ganglia, and potential synaptic regulation of endocrine functions. Studies will be performed using rodent, large mammal, and human tissues to allow for interspecies comparisons. Sex as a biological variable will also be included in the studies. The TEM service will work closely with each participating SPARC laboratory and provide advice on tissue harvesting and preservation as well as perform tissue processing and embedding of tissues in plastic resin, semi-thin and ultrathin sectioning for ultrastructural studies, TEM of nervous tissues, pre- and post-embedding immuno-EM studies, quantitative analysis of nerves, ganglia, neural circuits, and synaptic structures, customization of TEM protocols to accommodate project specific needs, and interpretation of ultrastructure and quantitative TEM data. It is expected that the proposed TEM studies will add value to SPARC-funded investigations and augment interpretability of functional and modeling studies as well as provide critical ultrastructural data for an evidence-driven approach to the development of new and improved neuro-modulatory strategies.

项目摘要/摘要 器官功能可以通过刺激外周活动和靶向来调节，例如， 周围神经和自主神经节。然而，详细的功能和解剖组织是 对涉及内脏功能的自主神经、神经节和器官了解不多。意义重大 在许多器官功能的神经控制方面存在知识空白，包括那些 心脏、呼吸系统、下尿路和胃肠系统。更好地理解 周围器官的神经回路和神经支配的各种组件是必要的，以便 提供改进的设备建模和设计，以允许对选定器官功能进行最佳调制。 利用透射电子显微镜可以鉴定神经组织的精细结构。 为了表征，例如，轴突组成和髓鞘形成，神经回路的组织 自主神经节和自主神经靶点的神经支配。 拟议的研究将旨在为调查人员建立一个瞬变电磁服务，由 刺激外周活动缓解疾病(SPARC)联盟。 共有6个由南盟资助的项目，其中包括7个南盟下属的调查实验室， 已经确定了对透射电子显微镜研究的明确需求。这些项目包括对自主控制的研究 心脏，脑-肠道相互作用，舌下神经-对呼吸的影响，下尿路功能， 葡萄糖的神经内分泌调节，以及迷走神经功能的模拟。TEM研究将包括 内脏神经和躯体神经中有髓和无髓轴突的详细特征以及 自主神经节的组织，以及潜在的内分泌功能的突触调节。研究将会是 使用啮齿动物、大型哺乳动物和人类组织进行物种间比较。性爱是一种 生物变量也将包括在研究中。过渡时期服务将与每个人密切合作 参与SPARC实验室，并就组织采集和保存以及 在塑料树脂中进行组织加工和组织包埋，半薄和超薄切片 超微结构研究，神经组织的透射电子显微镜，包埋前后的免疫-EM研究，定量 分析神经、神经节、神经回路和突触结构，定制瞬变电磁协议，以 适应项目的具体需要，解释超微结构和定量的透射电子显微镜数据。 预计拟议的瞬变电磁研究将增加由SPARC资助的调查的价值，并 增强功能和模型研究的可解释性，并提供关键的超微结构数据 以证据为导向的方法来开发新的和改进的神经调节策略。