Investigating descending control of walking

项目总结/摘要 大脑中的电路控制运动输出，以产生生存所需的精确行为。功能障碍 这些回路会导致破坏性的运动障碍，如帕金森病和肌萎缩侧索硬化症。 硬化症重要的是要了解大脑通常是如何控制行为的， 运动输出的特征被编码在单个神经元中，以及这些表征是如何组织的 在神经元群体中。这个K99/R 00提案将支持Helen Yang博士追求了解 运动控制，让她获得连接和建模的新技能，这将开辟创新的 探索这个问题的途径。实验将在指导期间开始（进行 在哈佛医学院神经生物学系雷切尔·威尔逊博士的实验室里）， 博士在获得独立职位后，杨的实验室。杨博士的长期职业目标是了解 通过探索神经电路结构和跨神经元的编码， 时间尺度，希望提供深入了解运动障碍和假肢的发展 和机器人技术，概括了大脑控制运动动作的特征。 博士Yang目前的研究已经确定了一些下行神经元（DN），它们的活动与 具有行走行为的特定特征。DNs从大脑投射到神经索， 大脑控制运动输出的瓶颈因此，理解它们的编码和组织将 揭示运动控制的基本原理。利用包括监测和操纵在内的方法 神经活动，行为跟踪，连接和建模，具体目标1将研究如何DN 具体目标2将研究DN如何控制向前行走。期间 在这个建议的指导阶段，杨博士将专注于3个特定的DN，但她将扩大她的研究， 在独立阶段的附加DN，并检查如何转向和前进DN一起工作， 控制行走。 灵活性是运动动作的一个重要特征，但神经元回路如何实现它仍然知之甚少。 具体目标3，在独立阶段进行，将通过研究如何研究步行的灵活性， DN活动和招募的模式在行为环境和内部状态中发生变化。总体看 这项提议中的实验将大大促进对大脑如何控制运动输出的理解。 并为杨博士在学术界获得独立地位铺平道路。

Project Summary/Abstract Circuits in the brain control motor output to generate the precise behaviors required for survival. Dysfunction of these circuits results in devastating movement disorders such as Parkinson’s disease and amyotrophic lateral sclerosis. It is important to understand how the brain normally controls behavior by understanding what features of motor output are encoded in individual neurons and how these representations are organized across a neuronal population. This K99/R00 proposal will support Dr. Helen Yang in her pursuit to understand motor control and allow her to acquire new skills in connectomics and modeling that will open up innovative avenues of exploration of this problem. The experiments will be initiated during the mentored period (carried out in Dr. Rachel Wilson’s lab in the Department of Neurobiology at Harvard Medical School) and continue in Dr. Yang’s own lab upon securing an independent position. Dr. Yang’s long-term career goal is to understand robustness and flexibility in motor control by exploring neural circuit architecture and encoding across timescales, with the hope of providing insight into movement disorders and for the development of prosthetics and robotics that recapitulate features of the brain’s control of motor action. Dr. Yang’s current research has identified a number of descending neurons (DNs) whose activity is correlated with specific features of walking behavior. DNs project from the brain to the nerve cord and are a key bottleneck in the brain’s control of motor output. As such, understanding their encoding and organization will reveal fundamental principles of motor control. Utilizing approaches including the monitoring and manipulation of neural activity, behavior tracking, connetomics, and modeling, Specific Aim 1 will investigate how DNs control turns during walking, and Specific Aim 2 will investigate how DNs control forward walking. During the mentored phase of this proposal, Dr. Yang will focus on 3 specific DNs, but she will expand her studies to additional DNs in the independent phase and examine how turning and forward DNs function together to control walking. Flexibility is a critical feature of motor actions, but how neuronal circuits implement it is still poorly understood. Specific Aim 3, carried out during the independent phase, will investigate flexibility in walking by studying how patterns of DN activity and recruitment change across behavioral contexts and internal states. Overall, the experiments in this proposal should significantly advance understanding of how the brain controls motor output and pave the way for Dr. Yang to secure an independent position in academia.