Watching a vertebrate brain learn and behave in a virtual environment

观察脊椎动物大脑在虚拟环境中学习和行为

• 批准号: 8704392
• 负责人: Florian Engert
• 金额: $ 84.5万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8704392
• 关键词: Addictive Behavior; Algorithms; Anesthetics; Animal Model; Animals; Behavior; Behavioral; Biological Assay; Biological Models; Biological Neural Networks; Brain; Cells; Clinical Research; Computers; Cues; Data; Development; Disease; Electrodes; Environment; Fishes; Laser Scanning Microscopy; Learning; Memory; Monitor; Motor Neurons; Neurons; Operant Conditioning; Optics; Paralysed; Patients; Pattern; Population; Preparation; Resolution; Stimulus; Suction; Swimming; System; Technology; Testing; Training; Transgenic Organisms; Visual; Work; Zebrafish; abstracting; addiction; awake; base; brain machine interface; calcium indicator; interest; learned behavior; relating to nervous system; sensory feedback; theories; tool; two-photon; virtual; water flow

DESCRIPTION Abstract: In order to study the neural basis of navigation, learning, and memory, it is important to simultaneously record the activity of large populations of neurons involved in execution of behavior. This has been difficult or impossible in awake, freely moving preparations and the anesthetics and paralytics used to facilitate recordings often alter or abolish the relevant behaviors. I propose to establish a fictive swimming assay that allows paralyzed larval zebrafish to navigate through- and interact with a virtual environment. The sensory feedback provided to the animals will consist of visual cues through video projection screens and water flow provided by a computer controlled valve system. The fish are allowed to control these stimuli via activity in their motor-neurons recorded by a set of external suction electrodes. This arrangement makes it possible for immobilized fish to navigate a virtual environment entirely through power of activity in their motorneurons. As a first step we will combine this assay with 2-photon laser-scanning microscopy and allow transgenic fish lines that express genetically encoded calcium indicators in all neurons to navigate through virtual environments while neuronal activity is monitored. The small size and perfect translucence of the larval zebrafish provides in principle no barrier or restriction to these recordings and thus we have access to the whole brain at single cell resolution during these behavioral tasks. We can thus independently monitor the activities of hundreds or thousands of neurons as animals navigate their virtual worlds. As a subsequent step we will implement different learning assays that the animals have to execute in this virtual environment. In principle this will allow us to follow the flow of neural information in a single animal, before, during and after specific training sessions. The large volumes of resulting data will be analyzed and distilled with automated algorithms and the results used to sketch out potential models of how animals store information in neural networks in order to generate adapted behaviors. Subsequently, we can apply specific manipulations using genetically encoded optic tools for activating and silencing targeted subsets of neurons to test and develop these emerging theories. This platform will offer an unprecedented ability to track and manipulate the large- and smallscale activity patterns that underlie innate as well as learned behaviors.

描述 摘要： 为了研究导航、学习和记忆的神经基础，重要的是 同时记录参与执行的大量神经元的活动， 行为这在清醒的、自由活动的准备工作中是困难或不可能的， 用于促进记录的麻醉剂和麻痹剂经常改变或取消相关的 行为。我建议建立一个虚构的游泳试验， 在虚拟环境中导航并与之互动。感官反馈提供给 这些动物将通过视频投影屏幕和水流提供视觉提示 由计算机控制的阀门系统。鱼可以通过活动来控制这些刺激 在他们的运动神经元中，通过一组外部抽吸电极记录。这种布置 使固定的鱼完全通过能量在虚拟环境中导航成为可能。 运动神经元的活动。 作为第一步，我们将联合收割机与双光子激光扫描显微镜结合， 在所有神经元中表达遗传编码的钙指示剂的转基因鱼系， 在虚拟环境中导航，同时监测神经元活动。小尺寸和 斑马鱼幼鱼的完全透明性原则上不提供这些障碍或限制。 记录，因此我们可以在这些过程中以单细胞分辨率访问整个大脑。 行为任务因此，我们可以独立地监测数百或数千人的活动， 神经元就像动物在虚拟世界中导航一样。 作为后续步骤，我们将实施不同的学习试验，动物必须 在这个虚拟的环境中。原则上，这将使我们能够跟踪神经元的流动， 在特定训练期之前、期间和之后，在单个动物中的信息。 将使用自动算法分析和提取大量由此产生的数据， 这些结果被用来勾勒出动物如何在神经系统中存储信息的潜在模型， 网络以产生适应性行为。随后，我们可以应用具体的 使用基因编码的光学工具激活和沉默靶向亚群的操作 来测试和发展这些新兴的理论。 该平台将提供前所未有的能力来跟踪和操纵大型和小型 这些活动模式是先天行为和后天行为的基础。