CAREER:A Multidisciplinary Approach to Unraveling the Neural Circuits that Govern Odor Modulation of Locomotion and to Improving Neuroscience Education

一项简单的任务，比如走到一个人最喜欢的咖啡店，需要进行几个时间尺度的计算。在短时间尺度(不到1秒)，一个人必须在凹凸不平的表面上移动双腿并保持平衡；在中等时间尺度(几秒)，一个人必须在人行道上相对笔直地行走；在较长时间尺度(分钟)，一个人必须遵循街道标志或使用记忆导航；而在更长的时间尺度上，比如是否喝咖啡，你必须做出决定。首席研究员实验室的任务是使用新的技术，如创建行为的数学模型，开发新的方法来探测与行为有关的神经活动，以了解在多个时间尺度下潜在的行为的神经计算，当它们应用于给定任务时。这项拟议中的研究还具有重要的教育使命：世界上大多数问题都需要跨学科思维，而这种思维最好从小教授。在这个项目中，高中生直接参与了研究人员的多学科研究计划，目标是(1)深化学生的神经科学教育，重点放在工程、数学和技术上，(2)让他们在更年轻和更容易接受的年龄接受跨学科培训，(3)让他们做好全面思考复杂科学问题的准备。首席研究人员的主要研究目标是了解在复杂行为的执行过程中，大脑中感觉运动的变化是如何展开的，这些行为是动物自然行为的一部分。对这一过程的理解存在差距，因为解决这个问题需要一种综合的、多学科的方法，将神经科学技术、动物行为和计算技能结合起来--这种结合在一个研究人员身上并不常见。该项目的中心假设是，灵活的行为来自模块化的组织，可以分为两个神经子任务：(1)设计一个将感官反应转化为行动的“行动计划”；(2)使行动计划适应当前的需求，从而产生成功执行任务所需的行为灵活性。该项目在气味引导运动的背景下测试了这一假设，这是一种复杂的灵活行为，在一个相对简单且遗传上高度易驯化的模型系统--果蝇中进行。一个多学科的方法，包括数学建模，活体全细胞膜片钳记录，功能成像，和定量行为分析被用来解决中心假设。

A simple task like walking to one's favorite coffee shop involves computation across several timescales. On a short timescale (less than 1 second), one has to move one's legs on an uneven surface and maintain balance; on a medium timescale (a few seconds) one has to walk relatively straight on a sidewalk; on a longer timescale (minutes), one has to follow the street signs or use one's memory to navigate; and on an even longer timescale decisions such as whether or not to drink coffee are made. The mission of the principal investigator's laboratory is to understand neural computations underlying behavior at multiple timescales as they apply to a given task using novel techniques such as creating mathematical models of behavior and developing new methods for probing neural activity as it relates to behavior. The proposed research also has an important educational mission: Most problems in the world require interdisciplinary thinking, which is best taught at an early age. In this project, high school students are directly involved in the investigator's multidisciplinary research program, with the goals of (1) deepening the students' neuroscience education with a focus on engineering, mathematics, and technology, (2) exposing them to interdisciplinary training at a younger and more receptive age, and (3) preparing them well to think holistically about complex scientific problems. The overarching objective of the principal investigator's research is to understand how sensorimotor transformation unfolds in the brain during the performance of complex behaviors that are part of an animal's natural behavioral repertoire. The gap in understanding of this process exists because attacking this problem requires an integrated, multidisciplinary approach that combines neuroscience techniques, animal behavior, and computational skills- a combination not often found in one investigator. The central hypothesis of the project is that flexible behaviors emerge from a modular organization and can be divided into two neural subtasks: (1) to devise an "action plan" that transforms sensory responses into actions; and (2) to adapt the action plan to current demands and thereby generate behavioral flexibility needed for successful task execution. The project tests this hypothesis in the context of odor-guided locomotion, a complex flexible behavior, in a relatively simple and genetically highly tractable model system, Drosophila. A multidisciplinary approach that includes mathematical modeling, in vivo whole-cell patch clamp recordings, functional imaging, and quantitative behavioral analysis is employed to address the central hypothesis.