Investigating descending control of walking

研究步行的下降控制

• 批准号: 10708171
• 负责人: Helen Horan Yang
• 金额: $ 13.41万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10708171
• 关键词: Academia; Acceleration; Address; Amyotrophic Lateral Sclerosis; Animals; Architecture; Automobile Driving; Behavior; Behavior Control; Behavioral; Brain; Calcium; Cells; Characteristics; Code; Courtship; Development; Drosophila genus; Functional disorder; Goals; Hunger; Image; Individual; Investigation; Ipsilateral; Leg; Logic; Measures; Mediating; Mentors; Modeling; Monitor; Motor; Motor output; Movement; Movement Disorders; Nature; Nerve; Nervous System; Nervous System Physiology; Neurobiology; Neurons; Parkinson Disease; Pattern; Phase; Population; Positioning Attribute; Prosthesis; Research; Robotics; Satiation; Secure; Signal Transduction; Walking; Work; career; connectome; experience; experimental study; flexibility; fly; innovation; insight; medical schools; mind control; motor control; neural; neural circuit; neuronal circuitry; neuroregulation; novel; predictive modeling; recruit; skills; statistics

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.

项目概要/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。 这些回路会导致毁灭性的运动障碍，例如帕金森病和肌萎缩侧索硬化症 通过了解什么来了解大脑通常如何控制行为非常重要。 运动输出的特征被编码在单个神经元中以及这些表示是如何组织的 这项 K99/R00 提案将支持 Helen Yang 博士追求理解。 运动控制，让她获得连接组学和建模方面的新技能，这将开启创新 探索这个问题的途径将在指导期间启动（进行）。 哈佛医学院神经生物学系 Rachel Wilson 博士的实验室）并继续 获得独立职位后，杨博士自己的实验室是杨博士的长期职业目标。 通过探索神经电路架构和编码来提高运动控制的鲁棒性和灵活性 时间尺度，希望能够深入了解运动障碍和假肢的开发 以及概括大脑控制运动动作特征的机器人技术。 杨博士目前的研究已经确定了一些下行神经元（DN），其活动与 DN 具有步行行为的特定特征，从大脑投射到神经索，是关键。 因此，了解它们的编码和组织将成为大脑控制运动输出的瓶颈。 揭示电机控制的基本原理，包括监控和操纵。 神经活动、行为跟踪、神经经济学和建模的具体目标 1 将研究 DN 如何 行走期间控制转弯，特定目标 2 将研究 DN 在行走期间如何控制向前行走。 在该提案的指导阶段，杨博士将重点关注 3 个特定的 DN，但她将把她的研究扩展到 在独立阶段添加额外的 DN，并检查转向和转发 DN 如何一起发挥作用 控制行走。 灵活性是运动动作的一个关键特征，但人们对神经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，将通过研究步行的灵活性 DN 活动和招募模式会随着行为背景和内部状态的变化而变化。 该提案中的实验将显着促进对大脑如何控制运动输出的理解 为杨博士在学术界获得独立地位铺平道路。