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: 10152859
• 负责人: LEIF A HAVTON
• 金额: $ 39.91万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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 2023-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152859
• 关键词: Transmission; Electron; Microscopy; Service; SPARC

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.

项目总结/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 对自主神经、神经节和涉及内脏功能的器官的了解不多。显著 关于许多器官功能的神经控制存在知识差距，包括那些 心脏、呼吸系统、下泌尿道和胃肠道系统。更好地理解 需要神经回路和周围器官的神经支配的各种成分， 提供改进的装置建模和设计，以允许选择器官功能的最佳调节。 透射电子显微镜（TEM）允许识别神经组织的精细结构 为了表征例如轴突组成和髓鞘形成， 自主神经节和自主目标的神经支配。 拟议的研究将旨在为调查人员建立TEM服务， 刺激外周活动以缓解状况（Stimulating Peripheral Activity to Relieve Conditions，缩写为SEP）。 总共有6个由南太平洋区域研究中心供资的项目，其中包括7个南太平洋区域研究中心附属的调查实验室， 确定了TEM研究的明确需求。这些项目包括研究自主控制 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和迷走神经功能的建模。TEM研究将包括 内脏和躯体神经中有髓和无髓轴突的详细特征，以及 自主神经节的组织和内分泌功能的潜在突触调节。研究将 使用啮齿动物、大型哺乳动物和人类组织进行，以进行种间比较。性别作为 生物变量也将纳入研究。TEM服务将与每个 参与实验室，并提供有关组织采集和保存的建议，以及 进行组织处理，将组织包埋在塑料树脂中，半薄切片， 超微结构研究，神经组织的TEM，包埋前后的免疫EM研究，定量 神经、神经节、神经回路和突触结构的分析，TEM协议的定制， 满足项目的具体需求，并解释超微结构和定量TEM数据。 预计拟议的TEM研究将增加南太平洋区域研究中心资助的调查的价值， 增强功能和建模研究的可解释性，并提供关键的超微结构数据， 一个证据驱动的方法来开发新的和改进的神经调节策略。