CAREER: Neural mechanisms of flexible sensorimotor processing in C. elegans

大脑通过解读生物体周围的世界来指导其行动和运动，但大脑究竟是如何做到的仍然是一个谜。这个职业奖旨在研究小蠕虫的大脑如何探测到环境信息并将信息转化为行动。蛔虫的大脑很小，这使得研究信息流成为可能，因为信息流在大脑中穿行，其细节和完整性目前在其他更复杂的动物身上是不可能的。这项研究使用了首席研究员开发的新方法来记录蠕虫爬行时大脑的活动。这项研究的结果将为大脑如何灵活地处理信息和产生行动提供新的见解。这项工作与一项全面的教育和外联计划相结合。在其中一个环节，将为公共政策专业的学生举办实践研讨会，让他们了解基因工程和机器学习，这两项尖端技术使拟议的研究成为可能，也有可能改变社会。PI将研究线虫C.秀丽隐杆线虫感觉运动处理的电路水平机制。动物根据内部状态灵活地解释感觉信号来驱动马达输出。在某些状态下，施加的机械感觉信号将通过网络传播以引起运动反应，而在其他状态下则不会。这个项目使用全脑钙成像在细胞分辨率在自由移动秀丽隐杆线虫绘制功能路径的感觉信号传播。具体来说，这项工作旨在定位网络中机械感觉信号转化为运动信号的位置，并使用全脑方法识别状态信息在这条路径上的影响。秀丽隐杆线虫的神经系统紧凑，只有302个神经元，具有光学透明性，遗传易感性和映射的连接组，非常适合进行研究。这项研究资助的教育和推广部分针对的是公共政策专业的学生、来自代表性不足群体的物理学和工程学本科生，以及神经科学专业的本科生。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The brain interprets the world around an organism to guide its actions and movements, but exactly how the brain does so remains a mystery. This CAREER award seeks to study how the brain of a small worm detects information about its environment and transforms that information into actions. The worm's small brain makes it possible to study the flow of information as it traverses through the brain with a level of detail and completeness that is not currently possible in other more complicated animals. The investigation uses new approaches that the principal investigator developed to record activity of the worm's brain as it crawls. The results of this study will provide new insights into how brains flexibly process information and generate actions. The work is integrated with a comprehensive education and outreach plan. In one component, hands-on workshops will be held for public policy students to learn about genetic engineering and machine learning, two cutting-edge technologies that enable the proposed research and also have the potential to transform society.The PI will investigate circuit-level mechanisms underlying sensorimotor processing in the nematode C. elegans. The animal flexibly interprets sensory signals to drive motor outputs dependent upon internal state. In some states an applied mechanosensory signal will propagate through the network to elicit a motor response, while in other states it will not. This project uses whole brain calcium imaging at cellular resolution in freely moving C. elegans to map out the functional paths by which the sensory signals propagate. Specifically, the work seeks to locate where in the network mechanosensory signals transition into locomotory signals, and to identify where state information impinges on this path using a whole-brain approach. C. elegans, with its compact nervous system of only 302 neurons, optical transparency, genetic tractability and mapped connectome is well-suited to carrying out the investigation. Education and outreach components of this research grant target students of public policy, undergraduate physics and engineering students especially from underrepresented groups, and undergraduate neuroscience students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.