Independence of Spinal Motor Modules and Motoneuron Recruitment from Motor Modules: New Experimental Tests

脊髓运动模块的独立性和运动模块的运动神经元招募：新的实验测试

• 批准号: 10613306
• 负责人: Trevor Shawn Smith
• 金额: $ 4.75万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613306
• 关键词: Anatomy; Animals; Biology; Biomedical Engineering; Cells; Chronic; Clinical; Complex; Conscious; Creativeness; Disease; Electric Stimulation; Electrodes; Electromyography; Elements; Engineering; Exhibits; Freedom; Functional disorder; Generations; Goals; Health; Hindlimb; Human; Individual; Interneurons; Intuition; Investigation; Joints; Lampreys; Limb structure; Linear Models; Locomotion; Mathematics; Mediating; Methods; Mission; Modeling; Modification; Motor; Motor Activity; Motor Neurons; Movement; Mus; Muscle; Neurobiology; Neuromodulator; Neurons; Neurosciences; Neurotransmitters; Outcome; Pattern; Pattern Formation; Periodicity; Phase; Physiology; Population; Process; Property; Public Health; Quality of life; Rana; Rana catesbeiana; Reflex action; Research; Scientist; Signal Transduction; Site; Spinal; Spinal Cord; Spinal Manipulation; Spinal cord injury; Stereotyping; Structure; System; Techniques; Testing; Tetrapoda; Time; Training; Turtles; United States National Institutes of Health; Universities; Vertebral column; Vertebrates; Wheelchairs; Work; analog; career; clinical application; density; extracellular; flexibility; improved; innovation; insertion/deletion mutation; intraspinal microstimulation; motor behavior; motor control; motor disorder; neural correlate; neuroprosthesis; new technology; nonhuman primate; novel; pharmacologic; programs; recruit; response; restoration; skills; spinal reflex; synergism; tool; translational applications

Research Abstract The spinal cord appears, at least in part, to structure movement through combining a limited number of stereotyped ‘motor modules’. Module structure and combination is often dysfunctional in motor system diseases, such as spinal cord injury (SCI). The long-term goal of this research is to identify mechanisms of motor module structure and recruitment, to enable artificial activation or restoration to ameliorate maladaptive motor control. The objective of this proposal is to determine how spinal motor modules are activated in the spinal cord and how these modules then recruit motoneurons from the motor pools in the simpler spinal bullfrog model. The central hypothesis is that motor modules are partially independent, generate both rhythm and pattern, and recruit particular motoneurons across coactivated motor pools in turn. The rationale underlying this proposal is that frogs have unique physiology allowing chronic survival despite destruction of supraspinal centers, permitting the intrinsic capacities of the spinal cord to be studied within the intact musculature over an extended period of time. This proposal builds off historical research which activated motor modules through electrical stimulation or excitatory neurotransmitters. I will test the central hypothesis through two specific aims: 1) Evaluating independence of module activation during manipulation of spinal state, and 2) Discerning the granularity of recruitment of motor pools contributing to motor modules. I utilize two innovative methods to refine these investigations: 1) a new type of electrode which can record from many single motor units simultaneously and 2) a new mathematical tool to identify state-dependent effects between a spiking neuron with continuous signals, such as muscle activity. The proposed research is significant as it will bridge modularity research in the spinal wiping reflexes with hierarchical models of spinal motor pattern generation (e.g. locomotion). A more refined understanding of motor module organization may clarify muscle and motor pool recruitment in higher species, including humans, where direct analysis is often obscured or impossible due to increased complexity. The expected outcome of this work is an understanding of how modules are activated by the spinal cord and their capacity to be flexibly combined. This work will have a further positive impact by validating new tools and techniques for experimental use, and lay the groundwork for proactively activating motor modules in a task-dependent fashion in neuroprostheses. Towards this end, I have finished my neuroscience coursework and proposed cross-disciplinary training in biomedical engineering through Drexel University’s neuroengineering initiative to increase his quantitative skills to better pursue these questions. This training plan will combine the historically-strong program of spinal cord biology and motor control within the Department of Neurobiology and Anatomy with the quantitative rigor of formal mathematics and engineering, further equipping me to accomplish these aims and pursue a successful career as an independent research scientist.

研究摘要 脊髓至少部分地通过组合有限数量的神经元来进行结构运动。 刻板的“运动模块”在运动系统中的模块结构和组合通常是功能失调的。 这项研究的长期目标是确定脊髓损伤（SCI）等疾病的机制。 运动模块结构和募集，以实现人工激活或恢复以改善适应不良 该提案的目的是确定脊髓运动模块是如何激活的。 脊髓以及这些模块如何从更简单的脊髓的运动池中招募运动神经元 牛蛙模型的中心假设是运动模块是部分独立的，产生两种节律。 和模式，并依次在共激活的运动池中招募特定的运动神经元。 这一提议的基础是，青蛙具有独特的生理机能，可以在环境遭到破坏的情况下长期生存。 脊髓上中心，允许在完整的脊髓内研究脊髓的内在能力 该提议建立在激活运动的历史研究的基础上。 我将通过电刺激或兴奋性神经递质来测试中心假设。 两个具体目标：1）评估脊柱状态操纵过程中模块激活的独立性， 2）辨别对运动模块有贡献的运动池招募的粒度。 改进这些研究的两种创新方法：1）一种新型电极，可以记录许多 同时单个运动单元和 2) 一种新的数学工具，用于识别单个运动单元之间的状态相关效应 具有连续信号的尖峰神经元，例如肌肉活动，这项研究意义重大。 脊柱擦拭反射的模块化研究与脊髓运动模式的分层模型的桥梁 对运动模块组织的更精细的理解可能会阐明肌肉。 以及包括人类在内的高等物种的运动池招募，直接分析常常被掩盖或 由于复杂性增加而不可能。这项工作的预期结果是了解如何进行。 模块由脊髓激活，并且它们具有灵活组合的能力。 通过验证实验使用的新工具和技术来产生进一步的积极影响，并为 为此，我以任务依赖的方式主动激活神经假体中的运动模块。 完成了我的神经科学课程并提出了生物医学工程的跨学科培训 通过德雷克塞尔大学的神经工程计划来提高他的定量技能，以更好地追求这些 该培训计划将结合历史悠久的脊髓生物学和运动项目。 神经生物学和解剖学系内的控制具有形式数学的定量严谨性 和工程，进一步使我能够实现这些目标并追求成功的职业生涯 独立研究科学家。