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.

抽象的： 核心 C 将协助该项目的总体目标测试以下统一假设：衰老的听觉神经元和 它们的亚细胞成分发生明确的结构改变，导致深刻的神经回路重新布线 以及听觉通路上异常的结构/功能可塑性。 Core C将利用国家中心 显微镜和成像研究（NCMIR；Perkins 博士）资源和 Fritzsch 博士的共焦显微镜 和深入的神经解剖学专业知识。 Core C将利用计算机资源来集成大容量、微型和 通过串行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（生物标记物），进入每个项目以破译 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： 项目 1： 螺旋神经节神经元 (SGN) 从内毛细胞 (HC) 到毛细胞的结构（解剖）投射的研究 脑干耳蜗核 (CN)，使用 SBEM 显示年龄依赖性脱髓鞘和突触病变； 从耳蜗 HC 到 CN 的 SGN 亚型特异性投影追踪，以及年龄依赖性的确定 使用 SGN 亚型生物标志物的荧光标签重新布线。 Core C 将分析轴突节点和节间 使用 Nav 或 Kv3.1 和 CASPR 免疫荧光标记沿着外周听觉神经元 (AN) 进行检测。其他 将检查老化 SGN 的亚细胞变化。项目2：耳蜗核衰老研究 (CN) 使用 SBEM；突触小泡密度和线粒体结构的研究，具有深刻的年龄- ARHL 模型中依赖的突触可塑性。项目 3：神经纤维、突触的连接组学分析 中枢神经系统和梯形内侧核随着年龄的增长而改变的树突和线粒体网络 使用 SBEM 的身体 (MNTB)；跟踪相对较长的髓鞘厚度和节间长度 有髓轴突（AN 的中心部分和 MNTB 的浓密细胞轴突）。对于所有项目， 通常，大型共焦和 SBEM 体积将放置在 NCMIR 细胞图像库 (CIL) 中，从而允许 Core 项目研究人员对卷中的特征进行注释并跨站点共享注释以供查看 与其他地方经批准的研究人员交互地使用 CIL Web 应用程序。 Core C将支持整体 目标是为当前衰老听觉突触和神经序曲的知识差距提供新的见解 神经元，以确定 ARHL 的机制和治疗。