The Mouse Connectome Project Phase III: Assembling the global neural networks of the mouse brain

小鼠连接组项目第三阶段：组装小鼠大脑的全局神经网络

• 批准号: 10226677
• 负责人: Hong-Wei Dong
• 金额: $ 78.37万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-06 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10226677
• 关键词: Mouse; Connectome; Project; Phase; III

PROJECT SUMMARY/ABSTRACT The objective of our Mouse Connectome Project at USC (MCP) is to chart the long-range connectivity of ~800 delineated structures of the mouse brain in an effort to reveal its network organization. In Phase I (2009-2010), we established an efficient data production, collection, and image processing workflow dedicated to compiling connectomics data of the highest quality. We adopted an injection strategy that produced data most conducive for network analysis by simultaneously revealing, for any brain region (i.e. A), its (1) inputs (AB); (2) outputs (AB); (3) reciprocal or recurrent connections (AB); and (4) intermediate stations, which bridge brain structures that are not directly connected (ACB). In Phase II (2011-2016), we traced ~2000 pathways from injections placed across the entire cerebral hemisphere and thalamus. As proposed, in Phase III (2017-2022) we will collect and analyze connections data for the hypothalamus, midbrain, pons, medulla, and cerebellum (~1400 additional pathways) (Specific Aim 1). Combined, these pathways will be used to construct the most comprehensive mesoscale connectome that charts all point-to-point connections of the entire mouse brain. Compiling these connectivity data sets however is only the first step in constructing the connectome. The ensuing challenge is to analyze the enormous data to extract information regarding network organization. Based on graph theoretical analysis of 600 manually annotated pathways, we assembled the global networks of the mammalian neocortex (Zingg et al., Cell, 2014). Although the gold standard, manual analysis was laborious, time consuming, and not efficient for our ultimate goal of generating brain-wide connectivity maps and networks. Therefore, in Phase II, we designed and created an innovative informatics workflow that efficiently and reliably registers, reconstructs, and annotates large-scale connections data. This workflow will be applied in Phase III to accelerate image processing, creation of connectivity maps, data annotation, and analysis. In Phase III, we will also initiate the first stage of constructing cell type specific neural networks (Specific Aim 2). Our connectivity-based cell type classification strategy will be used to identify all cell types of the medial prefrontal cortex and to gain a census of each cell type using 2D and 3D images. Novel rabies viral tracing will be employed to systematically reveal the neuronal inputs to these distinct cell populations. All of our data will be available as open resources (www.MouseConnctome.org) (Specific Aim 3): (1) the iConnectome viewer is the only visualization tool that allows users to view images of multiple fluorescently-labeled pathways within their own bright-field Nissl background and corresponding level of a standard mouse brain atlas; (2) the iConnectome Map Viewer allows access to connectivity maps, which feature hundreds of reconstructed pathways compiled atop a neuroanatomic frame; (3) the iConnectome Cell Type Viewer, which will feature images of all cell type circuits; (4) the Cell Type Map Viewer will host cell type specific connectivity maps; (5) the online Web Connectivity Matrix will present connections in a matrix; and (6) our 3D viewer will provide an overview of all connections in 3D.

项目摘要/摘要 USC（MCP）的鼠标Connectome项目的目的是绘制〜800的远程连接 描绘了鼠标大脑的结构，以揭示其网络组织。在第一阶段（2009-2010）中， 我们建立了一个有效的数据生产，收集和图像处理工作流，专门用于编译 最高质量的连接数据。我们采用了一种产生数据最导数据的注射策略 为了进行网络分析，简单地揭示了任何大脑区域（即a），其（1）输入（AB）； （2）输出 （a选）; （3）相互或复发连接（AB）； （4）中间站，脑大脑 未直接连接的结构（aCb）。在第二阶段（2011-2016）中，我们从 注射遍布整个脑半球和丘脑。如提议，在第三阶段（2017-2022）中 我们将收集和分析下丘脑，中脑，PON，髓质和小脑的连接数据 （〜1400个其他途径）（特定目标1）。结合在一起，这些途径将用于构建最多的途径 全面的中尺度连接组图表了整个鼠标大脑的所有点对点连接。 但是，编译这些连接数据集只是构建连接组的第一步。随之而来的 挑战是分析大量数据以提取有关网络组织的信息。基于图 600手动注释途径的理论分析，我们组装了哺乳动物的全球网络 NeoCortex（Zingg等，Cell，2014）。尽管金标准，但手动分析是实验室，耗时，但 对于我们生成大脑范围的连通图和网络的最终目标而言，这并不有效。因此，在 第二阶段，我们设计并创建了一个创新的信息工作流，该工作流有效，可靠的寄存器， 重建并注释大规模连接数据。该工作流将在第三阶段应用以加速 图像处理，连接图的创建，数据注释和分析。在第三阶段，我们还将启动 构建细胞类型特定神经网络的第一阶段（特定目标2）。我们的基于连接性的单元格 分类策略将用于识别介质前额叶皮层的所有细胞类型，并获得 每种单元格类型都使用2D和3D图像。新颖的狂犬病病毒追踪将被系统地揭示 这些不同细胞群体的神经元输入。我们所有的数据将作为开放资源可用 （www.mouseconnctome.org）（特定目的3）：（1）IconNectome查看器是唯一的可视化工具 允许用户在自己的明亮场NISSL中查看多个荧光标记的途径的图像 标准小鼠大脑图集的背景和相应水平； （2）Iconnectome Map查看器允许 访问连接图，这些图具有数百种重建的途径，这些途径编译了神经解剖 框架; （3）Iconnectome细胞类型查看器，它将具有所有单元格电路的图像； （4）细胞类型 地图查看器将托管小区类型特定的连接图； （5）在线Web连接矩阵将存在 矩阵中的连接； （6）我们的3D查看器将概述3D中的所有连接。