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.

总结 这项雄心勃勃的计划将建立一个综合的实验-计算平台， 非人类灵长类动物普通绒猴的全脑中尺度连接图 （Callithrix jacchus），.它将通过追踪RNA条形码识别的神经元的轴突投射来实现这一点。 绒猴，利用基于测序的成像方法，也允许同时转录组细胞 识别神经元的类型。这将有助于弥合全脑中尺度连通性数据之间的差距 可用于小鼠从十年的测绘工作，使用现代技术和缺乏 人类和NHP的可比数据。 该提案将把新的基于病毒条形码的方法与基于示踪剂注射的方法结合起来。 收集前所未有的数据集的方法， 在具有细胞类型特异性的绒猴脑中的轴突投射，将这些数据应用于以下科学问题 灵长类动物和啮齿类动物之间的大脑连接如何不同，解决MRI衍生的 地面实况连通性的措施，并利用基于网络的工具使研究界参与 注释和使用结果数据。由世界领先的专家和问题先驱组成的多元化团队 领域谁已经合作，跨越不同的机构和学科，并配备了 优秀的设施和资源，将聚集在一起，组装使能平台。有五个具体的 旨在实现既定目标。目的一是建立中尺度投影成图的数据采集平台 在绒猴中使用条形码化+荧光AAV/AAV-retro。目的二是建立全脑范围的单轴突投射 使用全身注射与同步转录组细胞分型进行映射。目标3：开发数据 管理和分析管道。目的4是进行中尺度连通性的比较研究， 绒猴和小鼠，比较基于MRI的连接与地面实况。目标5是开发平台， 数据传播、通过门户网站的社区参与、协作校对和注释。 这样的数据集将具有深远的科学意义，可与灵长类动物的第一个全基因组图谱相媲美。 正如基因组编码理解生物体表型的蓝图一样，大脑的结构也是如此。 电路包含了解释动物行为的蓝图，并掌握着许多悬而未决的问题的关键。