Structural Analyses Core

结构分析核心

• 批准号: 10496283
• 负责人: GUY A PERKINS
• 金额: $ 33.1万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10496283
• 关键词: 3-Dimensional; Address; Affect; Age; Aging; Anatomy; Auditory; Auditory area; Axon; Behavior; Biological Markers; Blinded; Brain; Brain Stem; CBA/CaJ Mouse; CNTNAP1 gene; Cell Nucleus; Cells; Chronology; Clinical; Cochlea; Cochlear nucleus; Communication; Computers; Confocal Microscopy; Data; Data Analyses; Dedications; Demyelinations; Dendrites; Dimensions; Disease; Electron Microscopy; Ensure; Event; Experimental Designs; FDA approved; Face; Fluorescence; Functional disorder; Goals; Hair Cells; Human Resources; Image; Image Analysis; Imaging Device; Immunofluorescence Immunologic; Inhibitory Synapse; Inner Hair Cells; Investigation; Joints; Knowledge; Label; Labyrinth; Length; Light; Link; Maps; Measurement; Medial; Microanatomy; Microscope; Microscopic; Microscopy; Mission; Mitochondria; Modeling; Molecular; Monitor; Mus; Myelin; Nature; Nerve Degeneration; Nerve Fibers; Neuroanatomy; Neurons; Online Systems; Outcome; Pattern; Peripheral; Persons; Pharmaceutical Preparations; Presbycusis; Proteins; Public Health; Pyramidal Tracts; Research; Research Personnel; Resolution; Resources; Scanning Electron Microscopy; Sensorineural Hearing Loss; Series; Site; Source; Speed; Structure; Synapses; Synaptic Vesicles; Synaptic plasticity; Technology; Testing; Therapeutic; Thick; Time; age related; aged; aging auditory system; aging population; auditory pathway; brain tissue; cellular imaging; connectome; cost effective; design; digital imaging; excitotoxicity; experimental study; image archival system; image visualization; insight; microscopic imaging; nano; nanoscale; neural; neural circuit; neural network; neuron loss; neurosensory; quantitative imaging; reconstruction; signal processing; spiral ganglion; synaptic function; synergism; tool; trapezoid body; web app

Abstract: Core C will assist the overall goal of the Projects to test the unifying hypothesis that aging auditory neurons and their subcellular components develop defined structural alterations, leading to profound neural circuit re-wiring and aberrant structure/function plasticity along the auditory pathway. Core C will leverage the National Center for Microscopy and Imaging Research (NCMIR; Dr. Perkins) resources and Dr. Fritzsch's confocal microscopy and deep neuroanatomy expertise. Core C will use computer resources to integrate large-volume, micro- and nano-scale structural investigations through serial block-face scanning electron microscopy (SBEM) and confocal microscope z-series of fluorescent-tagged proteins (biomarkers), into each Project in deciphering the structural correlates of age-related hearing loss (ARHL). Core C will provide structural support for: Project 1: Studies of structural (anatomic) projections of spiral ganglion neurons (SGN) from inner hair cells (HCs) to the brainstem cochlear nucleus (CN), which show age-dependent demyelination and synaptopathy using SBEM; SGN subtype-specific projection tracing from cochlear HCs to the CN, and determination of the age-dependent re-wiring using fluorescent-tags of SGN-subtype biomarkers. Core C will analyze axonal nodes and internodes along the peripheral auditory neurons (AN) using Nav or Kv3.1 and CASPR immunofluorescence labeling. Other sub-cellular changes in the aging SGN will be examined. Project 2: Studies of aging on the cochlear nucleus (CN) using SBEM; investigation of synaptic vesicle densities and mitochondrial structure, with profound age- dependent synaptic plasticity in ARHL models. Project 3: Connectomic analysis of nerve fibers, synapses, dendrites, and mitochondrial networks that are altered in aging in the CN and the medial nucleus of the trapezoid body (MNTB) using SBEM; tracking myelin thickness and the length of the internodes over relatively long tracts of myelinated axons (central portion of the AN and axons of bushy cells to the MNTB). For all projects, the typically large confocal and SBEM volumes will be placed in the NCMIR Cell Image Library (CIL), allowing Core and Project researchers to annotate features in the volumes and share the annotations across sites to view in the CIL web application interactively, and with approved researchers elsewhere. Core C will support the overall goal in providing new insights into the current knowledge gaps in synaptic and neural overtures in aging auditory neurons, to determine the mechanism and treatment of ARHL.

摘要： 核心C将协助项目的总体目标，以测试听觉神经元老化和 它们的亚细胞成分发生了明确的结构变化，导致了深刻的神经回路重新布线， 以及听觉通路沿着异常结构/功能可塑性。核心C将利用国家中心 用于显微镜和成像研究（NCMIR; Dr. Perkins）的资源和Dr. Fritzsch的共聚焦显微镜 和深厚的神经解剖学专业知识Core C将利用计算机资源整合大容量、微型和 通过连续块面扫描电子显微镜（SBEM）进行纳米级结构研究， 共聚焦显微镜z系列荧光标记蛋白质（生物标志物），进入每个项目在破译 年龄相关性听力损失（ARHL）的结构相关性。核心C将为以下项目提供结构支持： 螺旋神经节神经元（SGN）从内毛细胞（HCs）向耳蜗投射的结构（解剖）研究 脑干耳蜗核（CN），使用SBEM显示年龄依赖性脱髓鞘和突触病; SGN亚型特异性耳蜗毛细胞到CN的投射追踪及年龄依赖性 使用SGN亚型生物标志物的荧光标签重新布线。核心C将分析轴突节点和节间 沿着周围听觉神经元（AN）使用Nav或Kv3.1和CASPR免疫荧光标记。其他 将检查老化SGN中的亚细胞变化。项目2：耳蜗核的老化研究 (CN)使用SBEM;研究突触囊泡密度和线粒体结构，具有深刻的年龄- 依赖性突触可塑性。项目3：神经纤维，突触， 树突和线粒体网络，在CN和梯形内侧核的老化中改变 使用SBEM的MNTB;在相对较长的纤维束上跟踪髓鞘厚度和节间长度 有髓轴突（AN的中心部分和MNTB的丛状细胞的轴突）。对于所有项目， 通常，大的共聚焦和SBEM体积将被放置在NCMIR细胞图像库（CIL）中， 和项目研究人员对卷中的要素进行注释，并跨站点共享注释，以便在 CIL网络应用程序交互，并与其他地方的批准研究人员。核心C将支持整体 目的是为老龄化听觉系统中突触和神经主动性的当前知识缺口提供新的见解。 神经元，以确定ARHL的机制和治疗。