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.

项目摘要/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。失调症 这些环路导致毁灭性的运动障碍，如帕金森氏病和肌萎缩侧索硬化 硬化症。了解大脑通常是如何通过理解什么来控制行为是很重要的 运动输出的特征在单个神经元中编码，以及这些表示是如何组织的 在神经细胞群体中。这份K99/R00提案将支持海伦·杨博士追求理解 运动控制，并让她在连接学和建模方面获得新技能，这将开启创新 探索这一问题的途径。实验将在指导期内启动(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中)，并继续 杨博士自己的实验室获得了一个独立的职位。杨博士的长期职业目标是了解 通过探索神经电路体系结构和编码实现电机控制的稳健性和灵活性 时间尺度，希望提供对运动障碍的洞察和假肢的发展 以及重述大脑控制运动动作的特征的机器人。 杨博士目前的研究已经确定了一些活动相关的下行神经元(DN) 具有特定的行走行为特征。从大脑到神经索的DNS投射是一个关键 大脑控制运动输出的瓶颈。因此，了解它们的编码和组织将 揭示马达控制的基本原理。利用包括监控和操纵在内的方法 在神经活动、行为跟踪、连接组学和建模方面，特定目标1将调查DNS如何 在步行过程中控制转弯，《特定目标2》将调查域名系统如何控制向前行走。在.期间 在这个计划的指导阶段，杨博士将专注于3个具体的域名，但她将把她的研究扩展到 独立阶段的其他域名，并检查转发和转发域名如何共同发挥作用 控制行走。 灵活性是运动动作的一个关键特征，但神经元电路如何实现它仍然知之甚少。 在独立阶段进行的具体目标3将通过研究如何在行走中灵活地进行。 目录号码活动和招募的模式会因行为环境和内部状态而变化。总体而言， 这一提议中的实验应该会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。