The connectome and neurobiology of a novel model chordate, Ciona intestinalis

新型脊索动物模型的连接组和神经生物学，海鞘

• 批准号: 9904776
• 负责人: BANGALORE S MANJUNATH
• 金额: $ 53.83万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904776
• 关键词: Adaptive Behaviors; Address; Anatomy; Animal Model; Animals; Atlases; Behavior; Behavioral; Biological Models; Brain; Brain imaging; Caenorhabditis elegans; Cell Nucleus; Cells; Chordata; Ciona intestinalis; Complement; Computer Vision Systems; Cues; Data; Detection; Development; Dimensions; Electron Microscopy; Electrons; Foundations; Functional Imaging; Gene Transfer Techniques; Generations; Goals; Health; Human; Image; Image Analysis; Imagery; Individual; Investigation; Ions; Knowledge; Label; Larva; Light; Lighting; Link; Maintenance; Methods; Microscope; Midbrain structure; Modeling; Nervous System Physiology; Nervous system structure; Neuraxis; Neuroanatomy; Neurobiology; Neurons; Neurotransmitters; Organism; Output; Pathway interactions; Pattern; Phenotype; Photoreceptors; Play; Prosencephalon; Reporting; Research; Research Personnel; Resolution; Role; Scanning Electron Microscopy; Sensory; Sepharose; Sister; Spinal Cord; Stretching; Subcellular Anatomy; Swimming; Synapses; System; Tadpoles; Technology; Testing; Time; Transgenic Organisms; Urochordata; Variant; Vertebrates; base; behavioral response; behavioral study; body system; calcium indicator; cell type; comparative; confocal imaging; connectome; connectome data; digital imaging; experience; hindbrain; imaging modality; imaging study; improved; in vivo; innovation; insight; light intensity; microscopic imaging; multimodality; multiple data types; neural patterning; neuronal patterning; novel; relating to nervous system; spatial integration; stereotypy; temporal measurement; tool; voltage

A comprehensive understanding of nervous system function requires integration of multiple types of data, from behavioral to anatomical. Ultimately function can be reduced to the patterns of connectivity between cells and the activation of single neurons. In this application we propose a set of aims that makes use of a unique organism with optimal qualities for multimodal nervous system investigation: the simple chordate, Ciona intestinalis. The anatomy of the Ciona larval tadpole CNS shows strong conservation with the CNS of the vertebrates, including homologs of the forebrain, midbrain/hindbrain, and spinal cord. Despite these conserved vertebrate-like features the Ciona tadpole is barely 1 mm long and has only ~2500 cells. Moreover the tadpole CNS has only 177 neurons. While the development of the Ciona CNS has been the subject of investigation for many years, new research opportunities have opened with the recent completion of the Ciona tadpole CNS connectome from serial section electron microscopy. The overall goal of this proposal is to build from the connectome data to identify correlates of behavior at the level of single, identifiable neurons. This project will be the combined undertaking of three research groups with expertise in Ciona live imaging and transgenesis, computer vision and image analysis, and electron microscopy and Ciona neuroanatomy. Preliminary data presented here demonstrate that the transparency and small size of Ciona tadpoles make them ideal for live imaging of brain activity using genetically encoded Ca2+ or voltage indicators. The aims of this proposal will be, first, to expand Ciona as a model of nervous system function, including a detailed characterization of behavior, the generation of a brain atlas at cellular resolution, and the quantification of stereotypy in brain cellular anatomy and connectivity; and, second, to apply these new tools in the characterization of patterns of neuronal activity as Ciona larvae respond to sensory cues by taking advantage of state-of-the-art imaging and neural activity detection methods. The connectome makes specific and novel predictions about patterns of neural activity, and the relative simplicity of the Ciona CNS will provide an innovative system for validating such predictions. This project presents challenges in image acquisition, analysis, and multimodal integration that stretch the limits of current technology, but holds the potential to provide an unparalleled view of chordate CNS function spanning multiple levels, from behavioral to synaptic.

对神经系统功能的全面理解需要整合多种类型的数据，从 从行为到解剖。最终功能可以简化为细胞和细胞之间的连接模式 单个神经元的激活。在此应用程序中，我们提出了一组利用独特的目标 具有多模式神经系统研究最佳品质的生物体：简单脊索动物，Ciona 肠杆菌。玻璃海鞘幼虫蝌蚪中枢神经系统的解剖结构与海鞘幼虫蝌蚪的中枢神经系统具有很强的保守性。 脊椎动物，包括前脑、中脑/后脑和脊髓的同源物。尽管有这些保守 Ciona 蝌蚪具有类似于脊椎动物的特征，长度仅为 1 毫米，并且只有约 2500 个细胞。还有蝌蚪 中枢神经系统只有 177 个神经元。虽然 Ciona CNS 的发展一直是研究的主题 多年来，随着最近完成的 Ciona 蝌蚪中枢神经系统，新的研究机会出现了 来自连续切片电子显微镜的连接组。该提案的总体目标是建立 连接组数据来识别单个可识别神经元水平的行为相关性。该项目将 由三个在 Ciona 实时成像和转基因方面拥有专业知识的研究小组联合开展， 计算机视觉和图像分析，以及电子显微镜和 Ciona 神经解剖学。初步数据 这里展示的海鞘蝌蚪的透明度和小尺寸使其成为活体的理想选择 使用基因编码的 Ca2+ 或电压指示器对大脑活动进行成像。该提案的目标是， 首先，将 Ciona 扩展为神经系统功能模型，包括行为的详细表征， 以细胞分辨率生成脑图谱，并对脑细胞中的刻板印象进行量化 解剖学和连接性；其次，将这些新工具应用于神经元模式的表征 海鞘幼虫利用最先进的成像和神经系统对感官线索做出反应 活动检测方法。连接组对神经模式做出具体而新颖的预测 Ciona CNS 的相对简单性将提供一个创新系统来验证此类活动 预测。该项目在图像采集、分析和多模式集成方面提出了挑战 突破了当前技术的限制，但有潜力提供无与伦比的脊索动物中枢神经系统视图 功能跨越多个层面，从行为到突触。