The basic wiring diagram of the brain: a global mouse brain connectome Phase II (Administrative Supplement)

大脑的基本接线图：全局小鼠大脑连接组第二阶段（行政补充）

• 批准号: 9234226
• 负责人: Hong-Wei Dong
• 金额: $ 32.01万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-16 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9234226
• 关键词: Administrative Supplement; 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）：该提案是我们为创建C57Black/6J鼠标大脑的三维，类似Google Earth的数字连接组的努力的延续。目前，我们已经建立了以高通量，工业化方式的大规模，多荧光连通性数据进行制造，收集和处理的整个管道。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），该系统加快了数据管理并减少了人为错误。遵循公正的，系统的，立体定位的“基于网格”的方法，使用了经过验证的神经电路追踪技术的双重配置，我们一直在构建一个“骨架” Connectome Map（I阶段I），该图将构成大约1600个传入和400只动物的1600个传播途径。在这里提出的第二阶段中，我们将在使用1200只动物的精制“基于网格”的注射策略之后，不断生成大规模的超高分辨率连通性数据。这些注射的收集将产生4800个传入和4800个传出途径，从而使整个大脑覆盖范围。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的可搜索目录，可在其自己的明亮场NISSL染色的nissl染色的细胞卫生背景中进行高分辨率。 IconNectome伴随着全面的连接在线数据库（BAMS），该数据库使用户能够以矩阵格式映射复杂的神经元网络，并将其与可用于Rat，Monkey和Human的可用连接数据相关联。此外，由我们的信息团队开发的Iconnectome注释报告系统（ICAR）将为每个注射站点提供级别的注释信息。强大的信息学工具最终将使用户能够比较标准3D解剖框架中任何注射站点的连接模式。为此，在第二阶段中，我们将以图形方式重建连接所有大脑结构的神经途径，并将提供四个版本的小鼠Connectome Atlas（MCA）：（1）MCA1.0（Google Satellite和Google Street View），以显示高分辨率的多量化多量子，标记为“原始”“原始”成像数据； （2）MCA2.0（Google Map）将提供图形化的轴突途径并逆行标记的神经元； （3）MCA3.0（Google驾驶方向路线图）将是连接大脑结构的示意性连通路线图； （4）BAMS生成的神经网络的Connectome矩阵和类似桌子的图形表示，这还将为MCA3.0提供文本版本导航指令。所有四个版本将被同步并集成到同一框架中，这将使我们能够组装Google类似地球的Connectome Atlas的最终版本。尽管是一项巨大的事业，但我们的I阶段进步和我们在神经解剖学，脑成像和神经信息方面具有世界一流的专业知识的团队证明了我们在第三阶段提供完整的三维数字小鼠Connectome Atlas的能力。