Investigating descending control of walking

研究步行的下降控制

• 批准号: 10568039
• 负责人: Helen Horan Yang
• 金额: $ 13.43万
• 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/10568039
• 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 Physiology; Nervous system structure; Neurobiology; Neurons; Parkinson Disease; Pattern; Phase; Population; Positioning Attribute; Prosthesis; Research; Robotics; Secure; Signal Transduction; Walking; Work; Yang; career; connectome; experience; experimental study; flexibility; fly; innovation; insight; medical schools; mind control; motor control; neural circuit; neuronal circuitry; neuroregulation; novel; predictive modeling; recruit; relating to nervous system; 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 脑控制电动机输出中的电路会产生生存所需的精确行为 这些电路导致毁灭运动障碍，例如帕金森氏病和肌萎缩性侧面 硬化症。 电动机输出的特征是在单个神经元中编码的，以及如何组织这些代表 在神经元人群中。 电动机控制，让她获得连接组学和建模的新技能，并通过Open Upen Upen Upen Upen Upen Upen Upen Upen Upen 探索该问题的途径将在指导时期开始（携带） 在哈佛医学院神经生物学系Rachel Wilson博士的实验室中 Yang'g博士自己的实验室确保了独立职位。 通过探索神经电路结构并跨越编码运动控制的鲁棒性和灵活性 时间尺度，希望提供有关运动障碍和假肢发展的见解 和机器人技术能够重新计算大脑对运动动作的控制。 杨博士的当前研究已经确定了许多活动相关的降临神经元（DNS） 具有步行行为的特定特征。 大脑对电动机输出的控制中的瓶颈。 揭示电动机控制的基本原理。 神经活动，行为跟踪，康复学和建模，特定目标1将研究DNS 步行过程中的控制转弯，而特定的AIM 2将调查DNS如何控制前进行走。 杨博士将在这一建议的指导阶段，将重点放在3个特定的DNS上，但她将把学习扩展到 在独立阶段的其他DNS，并检查转动和向前DNS如何共同发挥作用 控制步行。 屈曲度是运动动作的关键特征，但是它仍然可以理解神经元电路。 在独立阶段进行的特定目标3将通过研究如何研究如何研究如何研究如何研究如何研究如何研究如何研究研究如何研究研究如何研究研究方式来研究如何研究如何研究如何研究如何研究如何研究研究如何研究研究如何研究研究方式来研究的灵活性。 跨行为环境和内部状态的DN活动和招聘变化的模式 该提案中的经验应大大提高人们对大脑如何控制电动机输出的理解 并为杨博士确保在学术界获得独立职位铺平道路。