Functional and cell-type specific axonal pathways in the primate brain

灵长类动物大脑中的功能和细胞类型特异性轴突通路

• 批准号: 10272370
• 负责人: R CLAY REID
• 金额: $ 153.57万
• 依托单位: ALLEN INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10272370
• 关键词: Alzheimer' s disease patient; Anatomy; Antibodies; Area; Atlases; Autopsy; Axon; BRAIN initiative; Biological Assay; Brain; Brain Diseases; Calcium; Cells; Censuses; Classification; Data; Data Set; Development; Diffusion Magnetic Resonance Imaging; Disease Marker; Electrodes; Functional Imaging; Functional Magnetic Resonance Imaging; Genes; Goals; Histologic; Human; Image; Individual; Institutes; Institution; Label; Macaca; Magnetic Resonance Imaging; Maps; Measures; Methodology; Methods; Modality; Molecular; Neurodegenerative Disorders; Neurons; Neurosciences; Optics; Parietal; Pathway interactions; Phase; Physiology; Play; Population; Primates; Program Appropriateness; Property; Prospective Studies; Protocols documentation; RNA; RNA Probes; Recording of previous events; Research; Resolution; Role; Specificity; Stream; Surface; Techniques; Technology; Testing; Tissues; Translating; United States National Institutes of Health; Visual Cortex; Visual system structure; Work; anatomic imaging; brain cell; brain tissue; brain volume; cell type; experimental study; human tissue; improved; in vivo; innovation; light microscopy; multimodality; multiphoton imaging; neural circuit; neuromechanism; nonhuman primate; novel; optical imaging; postsynaptic; programs; relating to nervous system; success; tool; transcriptomics; white matter

Project Summary/Abstract Over the past decade, there have been transformative advances in three areas of mammalian neuroscience. First, our ability to record from large populations of neurons has dramatically increased with the advent of new electrode technologies and improved multiphoton imaging. Second, the study of brain connections in their entirety, connectomics, has come into its own as a field. Most recently, there has been a revolution in the classification of neuronal types, largely by probing which genes are translated into RNA in cells (transcriptomics). What is lacking is a way to bring these three fields together, particularly in the studies of non-human primates and humans. The goal of the current RFA is to create innovative tools for use in humans and non-human primates. In particular, two suggested topics are to develop: (1) “novel methods for tagging individual neurons such that cellular components of a functional circuit can be explored” and (2) “innovative approaches to bridge scales of experimental approach. Studies that can explore molecular and cellular mechanisms of neural activity in broader contexts are encouraged.” To achieve these goals, we present an innovative approach to characterize neuronal cell types in macaques and humans, combining transcriptomics, inter-areal connectivity and functional studies at multiple scales, from individual neurons to entire brains. We will build the necessary tools to create integrated atlases of individual brains that combine six modalities into a common reference frame: (1) functional MRI, to measure functional properties of brain areas at 0.5-1 mm resolution, (2) widefield optical imaging, to map bulk neuronal activity at the cortical surface with ~100 µm resolution, (3) multiphoton calcium imaging, to map neuronal activity in individual neurons across multiple cortical areas, (4) diffusion tensor imaging (DTI), to map axonal tracts in the white matter with 0.5-1 mm resolution, (5) “axonal connectomics”, to map projections of individual myelinated axons from efferent cell bodies to their postsynaptic targets, and (6) multiplexed FISH, to assay transcriptomic identities of the same cells whose physiology and projection targets have been defined. Data from first three modalities will be collected, starting with in vivo studies of macaques and correlated with subsequent analysis of brain tissue with the last three modalities. Only the last three steps will be used in the study of human brain tissue, although functional MRI could, in principle, be obtained from research institutions with appropriate programs for prospective studies.

项目摘要/摘要 在过去的十年中，在哺乳动物神经科学的三个领域取得了变革性的进步。 首先，随着新的冒险，我们从大量神经元中记录的能力已经大大提高 电极技术和改进的多光子成像。其次，研究大脑连接的研究 劣质，连接组学已成为一个领域。最近，已经发生了一场革命 神经元类型的分类，主要是通过探测哪些基因在细胞中转化为RNA（转录组学）。 缺少的是将这三个领域融合在一起的一种方式，尤其是在非人类隐私的研究中 和人类。 当前RFA的目的是创建用于人类和非人类私人的创新工具。尤其， 两个建议的主题是开发：（1）“标记单个神经元的新方法，使得细胞 可以探索功能电路的组件”和（2）“用于桥梁尺度的创新方法 实验方法。可以探索较广泛的神经活性的分子和细胞机制的研究 鼓励环境。”为了实现这些目标，我们提出了一种创新的方法来表征神经元 猕猴和人类中的细胞类型，结合了转录组学，美园间连通性和功能研究 从单个神经元到整个大脑，在多个尺度上。我们将构建必要的工具来创建集成的 单个大脑的地图集，将六种方式结合到一个共同的参考框架中：（1）功能性MRI， 测量以0.5-1 mm分辨率的大脑区域的功能特性，（2）广场光学成像，以绘制批量 〜100 µM分辨率的皮质表面的神经元活性，（3）多光子钙成像，以映射 多个皮质区域的单个神经元中的神经元活性，（4）扩散张量成像（DTI），以映射 白质中的轴突区域，分辨率为0.5-1 mm，（5）“轴突连接术”，以绘制映射的投影 从高效的细胞体到其突触后靶标的单个髓鞘的轴突，（6）多路复用鱼到 已经定义了生理和投影靶标的同一细胞的测定转录组身份。 将收集来自前三种方式的数据，从猕猴的体内研究开始，并与 随后以最后三种方式对脑组织进行分析。在 人类脑组织的研究原则上可以从研究机构获得功能性MRI 有适当的前瞻性研究计划。