The basic wiring diagram of the brain: a global mouse brain connectome Phase II

大脑的基本接线图：小鼠大脑整体连接组第二阶段

• 批准号: 8997116
• 负责人: Hong-Wei Dong
• 金额: $ 67.1万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8997116
• 关键词: Anatomy; Animals; Architecture; Atlases; Attention deficit hyperactivity disorder; Autistic Disorder; Automobile Driving; Biological; Biological Neural Networks; Brain; Brain imaging; Brain region; Cataloging; Catalogs; Collaborations; Collection; Communities; Complement; Complex; Custom; Data; Databases; Efferent Pathways; Electronics; Ensure; Etiology; Funding; Genetic Recombination; Genome; Goals; Human; Human Genome Project; Image; Imagery; Informatics; Information Resources Management; Injection of therapeutic agent; Instruction; Knowledge; Label; Laboratories; Link; Management Information Systems; Maps; Mental Depression; Mental disorders; Methods; Monkeys; Mus; National Institute of Mental Health; Nervous system structure; Neural Pathways; Neuroanatomy; Neurons; Organism; Output; Pathway interactions; Pattern; Phase; Primates; Process; Production; Publishing; Rattus; Reporting; Research; Research Infrastructure; Resolution; Route; Schizophrenia; Site; Skeleton; Staining method; Stains; Structure; Synapses; System; Technology; Text; Tracer; Workload; base; connectome; data management; design; digital; innovative technologies; male; neural circuit; neuroinformatics; programs; relating to nervous system; skeletal; tool; ultra high resolution

DESCRIPTION (provided by applicant): This proposal is a continuation of our efforts to create a three-dimensional, Google Earth-like, digital Connectome atlas of the C57Black/6J mouse brain. Currently, we have established the entire pipeline for manufacturing, collecting, and processing large-scale, multi-fluorescent connectivity data in a high-throughput, industrialized manner. To track and organize these large-scale data, we have developed the Laboratory Information Management System (LIMS), which expedites data management and reduces human error. Following an unbiased, systematic, stereotaxic "grid-based" approach using double coinjections of proven neural circuit tracing technology, we have been constructing a "skeleton" Connectome map (Phase I), which will constitute about 1600 afferent and 1600 efferent pathways from 400 animals. In Phase II, proposed here, we will continuously generate large-scale, ultra-high-resolution connectivity data following a refined "grid- based" injection strategy using 1200 animals. The collection of these injections will generate a total of 4800 afferent and 4800 efferent pathways, enabling whole brain coverage. Further, in Phase I, we developed the revolutionary iConnectome visualization program (www.MouseConnectome.org) that features a searchable catalog of multi-fluorescent neural tracer injections available to view at high-resolution within their own bright- field Nissl-stained cytoarchitectural background. The iConnectome is accompanied by a comprehensive connectivity online database (BAMS) that enables users to map complex neuronal networks in a matrix format and to correlate them with connectivity data available for the rat, monkey, and human. In addition, the iConnectome Annotation Reporting System (iCARS), developed by our informatics team, will provide level by level annotation information for each injection site. Powerful informatics tools eventually will enable users to compare connectivity patterns of any injection site within a standard 3D anatomic frame. To do this, in Phase II, we will graphically reconstruct neural pathways that link all brain structures and will deliver four versions of the Mouse Connectome Atlas (MCA): (1) MCA1.0 (Google satellite and Google street view) for displaying high- resolution multi-fluorescent labeled "raw" imaging data; (2) MCA2.0 (Google Map) will provide graphically reconstructed axonal pathways and retrogradely labeled neurons; (3) MCA3.0 (Google driving direction Roadmap) will be the schematic connectivity route map that links brain structures; and (4) Connectome matrix and table-like graphic representation of neural networks generated by BAMS, which will also provide the text version navigation instructions for MCA3.0. All four versions will be synchronized and integrated into the same framework, which will enable us to assemble the ultimate version Google Earth-like Connectome atlas. Although an enormous undertaking, our Phase I progress and our team with world-class expertise in neuroanatomy, brain imaging, and neuroinformatics is a testament to our ability to deliver the completed three- dimensional digital mouse Connectome atlas in Phase III.

描述（由申请人提供）：该提案是我们努力创建 C57Black/6J 小鼠大脑三维、类似 Google 地球的数字连接组图谱的延续。目前，我们已经建立了以高通量、工业化方式制造、收集和处理大规模、多荧光连接数据的完整管道。为了跟踪和组织这些大规模数据，我们开发了实验室信息管理系统 (LIMS)，该系统可加快数据管理并减少人为错误。遵循公正、系统、立体的“基于网格”的方法，使用经过验证的神经回路追踪技术的双重共注射，我们一直在构建一个“骨架”连接组图（第一阶段），它将构成来自 400 只动物的约 1600 个传入通路和 1600 个传出通路。在本文提出的第二阶段中，我们将使用 1200 只动物，遵循完善的“基于网格”的注射策略，不断生成大规模、超高分辨率的连接数据。这些注射的集合将产生总共 4800 个传入通路和 4800 个传出通路，从而实现全脑覆盖。此外，在第一阶段，我们开发了革命性的 iConnectome 可视化程序 (www.MouseConnectome.org)，该程序具有可搜索的多荧光神经示踪剂注射目录，可在其自己的明场尼氏染色细胞结构背景下以高分辨率查看。 iConnectome 附带一个全面的连接在线数据库 (BAMS)，使用户能够以矩阵格式映射复杂的神经元网络，并将其与大鼠、猴子和人类可用的连接数据相关联。此外，我们的信息学团队开发的iConnectome注释报告系统（iCARS）将为每个注射部位提供逐级注释信息。强大的信息学工具最终将使用户能够在标准 3D 解剖框架内比较任何注射部位的连接模式。为此，在第二阶段，我们将以图形方式重建连接所有大脑结构的神经通路，并将提供四个版本的小鼠连接组图谱（MCA）：（1）MCA1.0（谷歌卫星和谷歌街景），用于显示高分辨率多荧光标记的“原始”成像数据； （2）MCA2.0（谷歌地图）将提供图形重建的轴突通路和逆行标记的神经元； （3）MCA3.0（Google驾驶方向路线图）将是连接大脑结构的示意性连接路线图； (4) BAMS生成的神经网络的连接组矩阵和表格图形表示，这也将为MCA3.0提供文本版本的导航指令。所有四个版本都将同步并集成到同一个框架中，这将使我们能够组装最终版本的类似 Google Earth 的 Connectome 图集。尽管是一项艰巨的任务，但我们第一阶段的进展以及我们在神经解剖学、脑成像和神经信息学方面拥有世界一流专业知识的团队证明了我们有能力在第三阶段提供完整的三维数字小鼠连接组图谱。