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

项目摘要/摘要 这个项目是四所大学的研究人员合作的，目的是研究大脑是如何 决定。当一个人或任何动物在世界上行走时，它必须不断地决定什么是 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 对于动物来说，很难或不可能检查决定翻译的神经机制 因为神经计算的复杂性，涉及的神经元的数量， 以及动物运动产生的物理变化的复杂性。要减少这三个问题 复杂性，这个项目研究了裸目软体动物Berghia的大脑做出的觅食决定 甜菜亚科。这种海懒只有不到7000个神经元，它们可以被识别为个体或成员 特定阶级的。这个项目将绘制出大脑(连接体)的所有突触连接 连续切片大脑，并从电子显微镜图像中重建神经元和突触。这个 大脑中每个神经元表达的RNA将被测序，并将它们的转录映射到每个神经元上 连接体中的神经元。这将允许神经调制连接被推断并覆盖在 突触连接，产生一个“神经调制体”。该项目将开发CRISPR/Cas9基因编辑 这种“非模型”生物体的技术，允许表达基因编码的传感器和激活剂 在神经元课上。决策过程将在半完整的闭环准备中进行观察，其中 动物的大脑控制着一个虚拟环境，大脑使用自己的神经导航 命令。通过使用电压敏感染料或基因编码，一次将记录多个神经元 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 要观察的电路。将使用数学和统计方法来分析这些动态网络。 其结果将是算法及其在海参大脑中的实现。然后该项目将检查 随着大脑和身体的生长和神经元的增加，这个电路是如何变化的。了解神经回路是如何 在继续发挥功能的同时增加神经元是一个与人类直接相关的重要基础研究问题 疾病是因为人类的成人神经发生与许多认知和情绪障碍有关。

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.