A 5-dimensional connectomics approach to the neural basis of behavior

行为神经基础的 5 维连接组学方法

• 批准号: 9791024
• 负责人: Paul S Katz
• 金额: $ 113.2万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9791024
• 关键词: 3-Dimensional; Affect; Algorithms; Anatomy; Animals; Automobile Driving; BRAIN initiative; Basic Science; Behavior; Biogenic Amines; Biological; Brain; CRISPR/Cas technology; Cell Separation; Cognition Disorders; Collaborations; Complex; Control Animal; Data Set; Decision Making; Development; Dimensions; Electron Microscopy; Electrons; Fluorescence; Future; G-Protein-Coupled Receptors; Gene Expression; Generations; Genes; Goals; Growth; High-Throughput Nucleotide Sequencing; Human; Image; In Situ; Individual; Interruption; Label; Laboratories; Link; Locomotion; Maps; Mathematics; Mental Health; Methodology; Microfluidics; Mood Disorders; Motor; Movement; Nervous system structure; Neuromodulator; Neurons; Neuropeptides; Organism; Output; Pathway Analysis; Pattern; Play; Preparation; Process; RNA; Recording of previous events; Research; Research Personnel; Resources; Role; Sensory; Specimen; Statistical Methods; Stimulus; Structure; Synapses; System; Techniques; Technology; Testing; Time; Transgenic Organisms; Translating; Translations; Universities; adult neurogenesis; analytical tool; base; behavioral outcome; connectome; connectome data; experience; experimental study; human disease; information processing; interest; mathematical methods; member; microscopic imaging; neural circuit; neurogenesis; neuromechanism; neuroregulation; neurotransmission; nudibranch; relating to nervous system; sea slug; sensor; theories; tool; transcriptome; transcriptome sequencing; virtual; virtual reality; voltage sensitive dye

Project Summary / Abstract This project is a collaboration between researchers at four universities to examine how the brain makes decisions. When a human or any animal moves through the world, it must make constant decisions about what to do next. These decisions are based on the state of the animal, its past history, and its future goals. In most animals, it is difficult or impossible to examine the neural mechanisms underlying the translation of a decision into an actual motor act because of the complexity of the neural computation, the number of neurons involved, and the complexity of the physical change produced by the movement of the animal. To reduce all three of these complexities, this project examines foraging decisions made by the brain of a nudibranch mollusc, Berghia stephanieae. This sea slug has fewer than 7000 neurons and they are identifiable as individuals or as members of particular classes. This project will map out all of the synaptic connectivity of the brain (the connectome) by serially sectioning the brain and reconstructing neurons and synapses from electron microscopic images. The RNA expressed by each of the neurons in the brain will sequenced and their transcriptomes mapped onto each neuron in the connectome. This will allow neuromodulatory connectivity to be inferred and overlaid on the synaptic connectivity, producing a “neuromodulome”. The project will develop CRISPR/cas9 gene editing techniques for this “non-model” organism, allowing genetically-encoded sensors and activators to be expressed in neuron classes. The decision-making process will be observed in a closed-loop semi-intact preparation where the brain of the animal controls a virtual environment that the brain navigates through using its own neural commands. Multiple neurons at a time will be recorded from using voltage-sensitive dyes or genetically-encoded sensors. This real-time neural spike activity will be mapped onto the connectome, allowing the dynamics of the circuitry to be observed. Mathematical and statistical methods will be used to analyze these dynamic networks. The result will be the algorithm and its implementation in the brain of the sea slug. The project will then examine how this circuit changes as the brain and the body grow and add neurons. Understanding how neural circuits add neurons while continuing to function is an important basic research question that links directly to human disease because adult neurogenesis in humans has been linked to many cognitive and mood disorders.

项目摘要 /摘要 该项目是四所大学的研究人员之间的合作，以研究大脑如何制作 决定。当人类或任何动物在世界各地移动时，它必须不断就什么做出决定 接下来做。这些决定基于动物的状态，其过去的历史及其未来目标。大多数 动物，很难或不可能检查决定的翻译基础的神经机制 由于神经功能的复杂性，涉及的神经元的数量， 以及动物运动产生的身体变化的复杂性。减少这三个 复杂性，该项目考试觅食的决定由裸体软体动物的大脑做出的决定 斯蒂芬尼亚。该海sl弹的神经元少于7000，它们可以识别为个人或成员 特定的课程。该项目将通过 从电子显微镜图像中串行大脑并重建神经元和突触。这 由大脑中每个神经元表达的RNA将测序，并将其转录组映射到每个 连接组中的神经元。这将使神经调节连通性被推断并覆盖 突触连通性，产生“神经调节组”。该项目将开发CRISPR/CAS9基因编辑 这种“非模型”生物的技术，允许表达遗传编码的传感器和激活剂 在神经元课程中。决策过程将在闭环半完整准备中观察到，其中 动物的大脑控制着一个虚拟环境，大脑通过使用自己的中性 命令。一次将通过使用电压敏感染料或遗传编码来记录多个神经元 传感器。这种实时的神经尖峰活动将映射到连接仪上，从而允许 要观察的电路。数学和统计方法将用于分析这些动态网络。 结果将是算法及其在海sl的大脑中的实现。然后该项目将检查 该电路如何随着大脑和身体的成长和添加神经元而变化。了解中性电路 在继续发挥功能的同时添加神经元是一个重要的基础研究问题，直接与人类联系 疾病是因为人类的成年神经发生与许多认知和情绪障碍有关。