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.

项目总结/摘要 这个项目是四所大学的研究人员合作进行的，旨在研究大脑是如何使 决策当一个人或任何动物在世界上移动时，它必须不断地决定要做什么。 接下来要做的事这些决定是基于动物的状态，过去的历史和未来的目标。在大多数 在动物中，很难或不可能检查决定翻译背后的神经机制。 因为神经计算的复杂性，涉及的神经元的数量， 以及动物运动所产生的物理变化的复杂性。为了减少这三个因素， 复杂性，这个项目研究了裸鳃类软体动物Berghia大脑的觅食决定 千金藤族。这种海蛞蝓只有不到7000个神经元，它们可以被识别为个体或成员。 特定的类。这个项目将绘制出大脑的所有突触连接（连接体）， 连续切片大脑并从电子显微镜图像中重建神经元和突触。的 将对大脑中每个神经元表达的RNA进行测序，并将其转录组映射到每个神经元上。 连接体中的神经元。这将允许神经调节连接被推断并覆盖在 突触连接，产生一个“神经模块”。CRISPR/cas9基因编辑 这种“非模式”生物的技术，允许表达基因编码的传感器和激活剂， 在神经元课堂上。决策过程将在闭环半完整的准备中观察， 动物的大脑控制着一个虚拟的环境，大脑使用自己的神经网络在其中导航， 命令.多个神经元在同一时间将被记录从使用电压敏感染料或遗传编码 传感器.这种实时的神经尖峰活动将被映射到连接体上，从而允许神经元的动态变化。 要观察的电路。数学和统计方法将被用来分析这些动态网络。 结果将是算法及其在海蛞蝓大脑中的实现。该项目将审查 这个回路是如何随着大脑和身体的生长和神经元的增加而变化的。了解神经回路 添加神经元，同时继续发挥功能，是一个重要的基础研究问题，直接关系到人类 因为人类的成年神经发生与许多认知和情绪障碍有关。