Dissecting circuit and cellular mechanisms for limb motor control

剖析肢体运动控制的电路和细胞机制

• 批准号: 10522108
• 负责人: John Tuthill
• 金额: $ 107.19万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-17 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10522108
• 关键词: Action Potentials; Address; Algorithms; Animals; Architecture; Behavior; Behavioral; Behavioral Paradigm; Biological Models; Brain; Complex; Data; Drosophila genus; Drosophila melanogaster; Electron Microscopy; Electrophysiology (science); Engineering; Equipment and supply inventories; Exhibits; Feedback; Femur; Fire - disasters; Flexor; Foundations; Genetic; Goals; Interneurons; Intervention; Investigation; Joints; Label; Lead; Learning; Leg; Limb structure; Locomotion; Measurement; Measures; Mechanics; Modeling; Motor; Motor Neurons; Motor output; Movement; Muscle; Muscle Contraction; Nervous System Physiology; Nervous system structure; Neuraxis; Neuromuscular Diseases; Neurons; Output; Pattern; Physiology; Population; Positioning Attribute; Posture; Production; Property; Proprioceptor; Reflex action; Role; Signal Transduction; Spinal; Spinal Cord; Spinal Injuries; Stimulus; Structure; Synapses; System; Testing; Translating; Update; Vertebrates; Work; base; cell type; exhaustion; flexibility; fly; in vivo; insight; limb movement; motor control; motor neuron function; neural circuit; neural model; neural patterning; neuroregulation; novel; optogenetics; presynaptic neurons; reconstruction; recruit; relating to nervous system; sensory feedback; therapy design; tibia; tool; Action Potentials; Address; Algorithms; Animals; Architecture; Behavior; Behavioral; Behavioral Paradigm; Biological Models; Brain; Complex; Data; Drosophila genus; Drosophila melanogaster; Electron Microscopy; Electrophysiology (science); Engineering; Equipment and supply inventories; Exhibits; Feedback; Femur; Fire - disasters; Flexor; Foundations; Genetic; Goals; Interneurons; Intervention; Investigation; Joints; Label; Lead; Learning; Leg; Limb structure; Locomotion; Measurement; Measures; Mechanics; Modeling; Motor; Motor Neurons; Motor output; Movement; Muscle; Muscle Contraction; Nervous System Physiology; Nervous system structure; Neuraxis; Neuromuscular Diseases; Neurons; Output; Pattern; Physiology; Population; Positioning Attribute; Posture; Production; Property; Proprioceptor; Reflex action; Role; Signal Transduction; Spinal; Spinal Cord; Spinal Injuries; Stimulus; Structure; Synapses; System; Testing; Translating; Update; Vertebrates; Work; base; cell type; exhaustion; flexibility; fly; in vivo; insight; limb movement; motor control; motor neuron function; neural circuit; neural model; neural patterning; neuroregulation; novel; optogenetics; presynaptic neurons; reconstruction; recruit; relating to nervous system; sensory feedback; therapy design; tibia; tool

Motor neurons connect to muscles and comprise the major output of the nervous system. Patterns of neural activity in motor neurons cause temporally precise muscle contractions, producing coordinated and flexible behavior. These patterns are shaped by the connectivity and physiology of premotor circuits in the spinal cord that synapse onto the motor neurons. Premotor circuits combine descending motor commands with sensory feedback signals to drive motor neuron activity. How premotor networks are structured to control motor output is not well understood, due in part to an incomplete inventory of spinal cell types, and to the difficulties of recording neural activity in behaving animals. To address this gap, this project aims to use Drosophila melanogaster as a model for investigating motor control and premotor neural circuits. With an accessible and numerically compact nervous system, a large and growing suite of genetic tools, and agile, limbed locomotion, Drosophila has the potential to provide insight into fundamental problems of motor control. We introduce a task in which flies learn to generate specific amounts of force to position the femur-tibia joint in different targets. The joint is controlled by twelve neurons which can be genetically labeled for targeted neural recordings. Electrophysiological recordings will reveal how the complete population of motor neurons function together to dynamically position the leg and to sustain a given force output. These data will address long-standing hypotheses about how premotor circuits recruit subsets of motor neurons and the degree to which that control is flexible. Then, a new electron-microscopy level reconstruction of central locomotor circuits will allow identification of key premotor neurons. Electrophysiological recordings of those premotor neurons during the behavioral task will reveal their contributions to processing sensory feedback and to controlling leg force. These results will provide a foundation for understanding how descending commands interact with internal models of body state to control locomotion, a critical step toward achieving the long-term goals of designing interventions for neuromuscular disorders and algorithms for controlling engineered systems.

运动神经元连接到肌肉并构成神经系统的主要输出。模式 运动神经元中的神经活动会导致暂时精确的肌肉收缩，并产生协调 和灵活的行为。这些模式是由前电路的连通性和生理学形成的 在突触到运动神经元的脊髓中。前电路结合了下降电动机 具有感官反馈信号的命令，以驱动运动神经元活动。前网络的方式 尚不清楚以控制电动机输出的结构，部分原因是脊柱库存不完整 细胞类型，以及在行为动物中记录神经活动的困难。为了解决这个差距，这个 项目旨在将果蝇Melanogaster用作调查运动控制和前运动的模型 神经回路。具有可访问且数值紧凑的神经系统，一个大型且不断增长的套件 遗传工具和敏捷，肢体运动，果蝇有可能洞悉 电动机控制的基本问题。我们介绍了一项任务，苍蝇学会生成特定 将股骨 - 胫骨关节定位在不同靶标中的力量。关节由十二个控制 可用于靶向神经记录的神经元可以在遗传上标记。电生理记录 将揭示整个运动神经元的全部群体如何一起发挥作用，以动态定位 腿并维持给定的力量输出。这些数据将解决有关如何 前电路募集运动神经元的子集以及该控制的灵活程度。然后， 中央运动电路的新电子微观镜检查水平重建将允许识别钥匙 前神经元。行为任务期间这些前神经元的电生理记录 将揭示他们对处理感觉反馈和控制腿力的贡献。这些结果 将为理解下降命令如何与内部模型相互作用，为 控制运动的身体状态，这是实现设计长期目标的关键一步 用于控制工程系统的神经肌肉疾病和算法的干预措施。