秀丽线虫运动神经环路功能的全光学解析和计算模拟

项目名称： 秀丽线虫运动神经环路功能的全光学解析和计算模拟

项目编号： No.31471051

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 温泉

作者单位： 中国科学技术大学

项目金额： 90万元

中文摘要： 动物得以生存的必要条件之一是在不同外部环境和条件下灵活地调整运动节奏和方式。这需要运动神经系统整合感觉反馈信号来实现。然而我们对其中具体机理还知之甚少：这是因为对运动神经环路的理解主要基于对完全固定、麻醉或已解剖的动物体的研究，以至于破坏了各类感觉反馈对运动环路的调节。为克服此局限，本项目拟利用秀丽线虫模式系统，对运动神经环路的功能和动力学特性进行解析和模拟。在前期工作中，我们可以用钙成像和光遗传的手段对线虫神经元的生理活动进行测量、激活或抑制。在本项目的支持下，我们将进一步发展一套跟踪荧光显微镜技术，并整合光遗传手段，实现对自由移动线虫运动环路神经元的活动进行全光式的监测和操纵。通过微流器件，我们可以同时对感觉反馈做时间和空间上的控制。利用以上技术手段，并结合数学建模，我们希望解构秀丽线虫运动神经环路的动力学基础并深入阐明感觉反馈在运动控制中采用的算法和机制。

中文关键词： 光遗传学；神经环路；钙成像；本体感受；微流器件

英文摘要： To survive in different environments, animals must flexibly control their rhythmic motion and adapt their locomotory gaits. However, how neural circuit integrates external sensory feedback to drive animal movement remains poorly understood: the neuromuscular circuits have been mostly studied in immobilized, paralyzed or dissected preparations,where sensory feedback loops that modulate locomotion may no longer be functional. To overcome these obstacles, we propose to use C. elegans as a model system to investigate the neural circuit underlying motor control, to interrogate and model the whole motor circuit dynamics in a freely behaving animal. Previously, by utilizing tools in optogenetics and calcium imaging, we were able to measure, activate and inactivate C. elegans neuronal activities in vivo. In the next step, we will develop a fluorescence tracking microscope, when combined with optogenetic methods, will allow us to monitor and manipulate the activities of different neurons in the motor circuit of a freely moving worm. We will also develop microfluidic devices to perform defined spatiotemporal manipulation of sensory feedback. By combining novel experimental tools with mathematical modeling, we hope to deconstruct the motor circuit dynamics in C. elegans and to define the algorithms and mechanisms by which sensory feedback controls locomotion.

英文关键词： optogenetics;neural circuit;calcium imaging;proprioceptive feedback;microfluidic device