BRAIN CONNECTS: Comprehensive regional projection map of marmoset with single axon and cell type resolution

大脑连接：具有单轴突和细胞类型分辨率的狨猴综合区域投影图

• 批准号: 10664170
• 负责人: Guoping Feng
• 金额: $ 361.6万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-07 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664170
• 关键词: 3-Dimensional; Address; Animal Behavior; Animal Model; Animals; Architecture; Atlases; Axon; Bar Codes; Brain; Brain Diseases; Callithrix; Callithrix jacchus jacchus; Cells; Collaborations; Collection; Comparative Study; Data; Data Analytics; Data Set; Detection; Discipline; Dorsal; Genome; Genome Mappings; Goals; Human; Individual; Injections; Institution; Label; Magnetic Resonance Imaging; Maps; Measures; Methods; Modeling; Modernization; Motor Cortex; Mus; Neurons; Organism; Phenotype; Primates; Process; RNA; Research; Resolution; Resources; Rodent; Site; Skeleton; Specificity; Spottings; Structure; System; Techniques; Therapeutic; Titrations; Tracer; Validation; Viral; Visualization; blood-brain barrier crossing; brain circuitry; brain volume; cell type; community engaged research; community engagement; comparative; computational platform; data acquisition; data analysis pipeline; data dissemination; data management; frontal lobe; imager; imaging modality; in situ sequencing; neuronal cell body; nonhuman primate; prototype; reconstruction; scale up; transcriptomics; translational neuroscience; web platform; web portal; web-based tool; whole genome

SUMMARY This ambitious proposal will establish an integrated experimental-computational platform to create the first comprehensive brain-wide mesoscale connectivity map in a non-human primate, the common marmoset (Callithrix jacchus),. It will do so by tracing axonal projections of RNA barcode-identified neurons brain-wide in the marmoset, utilizing a sequencing-based imaging method that also permits simultaneous transcriptomic cell typing of the identified neurons. This will help bridge the gap between brain-wide mesoscale connectivity data available for the mouse from a decade of mapping efforts using modern techniques and the absence of comparable data in humans and NHP. The proposal will bring together new viral barcode-based approaches with established tracer-injection based methods to collect an unprecedented data set which will permit comprehensive mapping of region-to-region axonal projections in the marmoset brain with cell-type specificity, apply this data to scientific questions regarding how brain connectivity differs between primates and rodents, address the relation between MRI-derived measures to ground-truth connectivity, and utilize web-based tools to engage the research community in annotating and using the resulting data. A diverse team of world-leading experts and pioneers in the problem domain who are already collaborating, spanning diverse institutions and disciplines, and equipped with outstanding facilities and resources, will come together to assemble the enabling platform. There are five specific aims to achieve stated goals. Aim 1 is to establish data acquisition platform for mesoscale projection mapping in marmoset using barcoded + fluorescent AAV/AAV-retro. Aim 2 is to develop brain-wide single-axon projection maps using systemic injections with simultaneous transcriptomic cell-typing. Aim 3 is to develop data management and analysis pipelines. Aim 4 is to perform comparative studies of the mesoscale connectivity in marmoset and mouse, comparing MRI-based connectivity with ground truth. Aim 5 is to develop platforms for data dissemination, community engagement through web portal, collaborative proofreading and annotations. Such a data set will have profound scientific significance, comparable to the first whole genome map of a primate. As genomes encode the blueprint for understanding an organism’s phenotype, so does the architecture of brain circuitry contain the blueprint for explaining an animal’s behavior and holds the key to many open questions.

概括 这个雄心勃勃的建议将建立一个集成的实验计算平台，以创建第一个 非人类灵长类动物中的全面大脑范围的中尺度连通图 （Callithrix Jacchus），。它将通过追踪RNA条形码识别神经元的轴突投影在脑内 Marmoset，使用基于测序的成像方法，该方法也允许同时转录组细胞 识别神经元的键入。这将有助于弥合大脑范围的中尺度连接数据之间的差距 使用现代技术的十年来映射工作和缺乏 人类和NHP的可比数据。 该提案将通过既定的基于示踪剂注入的新的基于病毒条形码的方法来汇总新的基于病毒条形码的方法 收集前所未有的数据集的方法，该数据集将允许对区域到区域进行全面映射 具有细胞类型特异性的果果脑大脑中的轴突投射，将这些数据应用于科学问题 大脑连通性在素数和啮齿动物之间如何差异，解决MRI衍生之间的关系 采取基础真相连通性的措施，并利用基于Web的工具参与研究社区 注释并使用结果数据。一个世界领先的专家和开拓者的潜水团队 已经在合作，跨越潜水机构和学科的领域，配备了 出色的设施和资源将聚集在一起，组装启用平台。有五个特定的 旨在实现既定目标。 AIM 1是为中尺度投影映射建立数据采集平台 使用条形码 +荧光AAV/AAV-RETRO在果果中。 AIM 2是开发全脑部的单轴投影 使用具有简单转录组细胞型的全身注射的地图。目标3是开发数据 管理和分析管道。 AIM 4是对中尺度连接性进行比较研究 Marmoset和Mouse，将基于MRI的连接与地面真相进行比较。 AIM 5是为开发平台 数据传播，通过Web门户网站，协作校对和注释的社区参与。 这样的数据集将具有深刻的科学意义，与私人的第一个整个基因组图相媲美。 当基因组编码蓝图以理解有机体的表型时，大脑的结构也是如此 电路包含用于解释动物行为的蓝图，并拥有许多开放问题的关键。