Collaboratory for atlasing cell type anatomy in the female and male mouse brain

雌性和雄性小鼠大脑图谱细胞类型解剖学合作实验室

• 批准号: 9415873
• 负责人: Pavel Osten
• 金额: $ 253.65万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9415873
• 关键词: Address; Adult; Anatomy; Animals; Architecture; Area; Atlases; Axon; BRAIN initiative; Behavior; Brain; Brain region; Cell Density; Cells; Cellular Morphology; Censuses; Characteristics; Cognitive; Communities; Community Networks; Complex; Computing Methodologies; Data; Data Set; Development; Dimensions; Female; Gender; Gene Expression; Generations; Genes; Genetic; Hippocampus (Brain); Image; Imaging Device; Immunohistochemistry; In Situ Hybridization; Individual; Internet; Interneurons; Knowledge; Label; Laboratories; Location; Manuals; Methods; Microscopy; Modernization; Molecular; Morphology; Mus; Neuroglia; Neurons; Neurosciences; Pattern; Preparation; Protocols documentation; Reproductive Behavior; Research Infrastructure; Resolution; Scientist; Site; Standardization; Statistical Methods; Structure-Activity Relationship; Subcellular Anatomy; Synapses; System; Work; base; brain cell; cell type; collaboratory; computerized tools; density; male; method development; nerve supply; neuroinformatics; new technology; novel; postnatal; postsynaptic; rapid technique; reconstruction; response; sensory cortex; tool; web portal

Even though scientists have been captivated by the diversity of brain cells for well over a century, since the initial anatomical descriptions by Santiago Ramón y Cajal, it is only recently that the developments in new technologies allowed us to truly appreciate the astonishing complexity of cell types in the mammalian brain. Yet, even today, our knowledge of cell type anatomy and function is largely limited to a few brain areas, such as the sensory cortex or the hippocampus. This lack of whole-brain data has led to generalizations from one brain area to other regions with similar architecture. However, our preliminary studies applying quantitative whole brain analyses have revealed unexpected region specific differences in cell type ratios and uncovered new gender-based differences in cellular anatomy that can inform our understanding of brain development, wiring and function. We thus believe that closing the gaps in our knowledge of the cellular architecture of the brain will be a major contribution to enable a modern quantitative understanding of the brain as a system. Here we propose to establish an Anatomical Collaboratory for Systematic Atlasing of Cell-Type Distribution and Morphology in female and male brain. This Collaboratory will apply standardized, unbiased and largely automated methods developed in our laboratories to atlas the distribution and morphology of >80 molecularly defined cell classes and cell type across all regions of the female and male brain. This work will yield the most comprehensive characterization of cell type anatomy in the mammalian brain to date, establishing a structural basis for building an integrated Cell Type Brain Atlas. Specific Aim 1: Quantify and atlas the brainwide distribution of molecularly defined cell types. This work will generate a quantitative brain atlas of the distributions of molecularly defined cell classes and cell types within the Common Coordinated Framework (CCF) of the adult brain. Specific Aim 2: Quantify and atlas the brainwide morphologies of molecularly defined cell types. This work will generate a comprehensive structural brain atlas of somatodendritic cell-type morphologies across all CCF anatomical areas in the female and male brain. Specific Aim 3: Develop and deploy a neuroinformatics infrastructure: an integrated web portal for cell-type specific data, tools, and analytics. This work will disseminate the generated data via CSHL cell type-dedicated BrainArchitecture web portal and through the BRAIN Cell Data Center (BCDC). !

尽管科学家们对脑细胞的多样性着迷了世纪， 虽然圣地亚哥拉蒙·卡哈尔（Ramón y Cajal）最初的解剖学描述，但直到最近， 技术使我们能够真正理解哺乳动物大脑中细胞类型的惊人复杂性。 然而，即使在今天，我们对细胞类型解剖学和功能的了解在很大程度上也仅限于少数大脑区域，如 感觉皮层或海马体。由于缺乏全脑数据， 大脑区域与其他具有相似结构的区域。然而，我们的初步研究应用定量 全脑分析揭示了细胞类型比率中意想不到的区域特异性差异， 细胞解剖学中新的基于性别的差异，可以为我们理解大脑发育提供信息， 布线和功能。因此，我们相信，填补我们对细胞结构的知识空白， 大脑将是一个重大贡献，使现代定量了解大脑作为一个系统。 本文拟建立一个系统描述细胞型分布的解剖学协作实验室 以及男女大脑的形态学本次合作将采用标准化、无偏见、 在我们的实验室开发的自动化方法，以图谱的分布和形态>80分子 定义了男女大脑所有区域的细胞类别和细胞类型。这项工作将产生最大的收益 迄今为止，哺乳动物大脑中细胞类型解剖学的全面表征，建立了结构 建立一个综合的细胞类型脑图谱的基础。 具体目标1：量化和图谱的分子定义的细胞类型的全脑分布。这 这项工作将产生一个定量的大脑图谱，其中包括分子定义的细胞类别和细胞分布。 成人大脑共同协调框架（CCF）内的类型。 具体目标2：量化和图谱的分子定义的细胞类型的全脑形态。这 这项工作将产生一个全面的结构脑图谱的体树突细胞类型的形态， 女性和男性大脑中的CCF解剖区域。 具体目标3：开发和部署神经信息学基础设施： 细胞类型特定的数据、工具和分析。这项工作将通过CSHL细胞传播生成的数据 类型专用的BrainArchitecture门户网站和通过BRAIN Cell数据中心（BCDC）。 !