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 脊髓至少部分出现，以结合有限数量的构造运动 定型的“电动机模块”。模块结构和组合通常在电机系统中功能失调 疾病，例如脊髓损伤（SCI）。这项研究的长期目标是确定 电机模块的结构和招聘，以使人工激活或恢复以改善适应不良 电机控制。该提案的目的是确定如何在脊柱运动模块中激活 脊髓以及这些模块如何从更简单的脊柱中募集运动池的运动神经元 牛蛙模型。中心假设是运动模块部分独立，产生两个节奏 和模式，并又在共激活的电动池中募集特定的运动神经元。理由 该建议的基础是青蛙具有独特的生理学，允许长期生存任务破坏 脊柱上心的上心，允许脊髓的固有能力在完整的内部研究 长时间的肌肉。该提案建立了激活电动机的历史研究 通过电刺激或兴奋性神经递质的模块。我将通过 两个具体目的：1）评估脊柱状态操纵期间模块激活的独立性， 2）辨别出促成电动机模块的电动池募集的粒度。我利用 两种创新方法来完善这些投资：1）一种新型电极，可以从许多人那里记录 单电机单元和2）一种新的数学工具，以识别一个与状态依赖的效果 带有连续信号的尖峰神经元，例如肌肉活动。拟议的研究很重要，因为 脊柱擦拭反射的桥梁模块化研究，具有脊柱运动模式的分层模型 一代（例如运动）。对运动模块组织的更精致的了解可能会阐明肌肉 在包括人类在内的高等物种中招募的电动池招募，在这些物种中，直接分析通常被遮盖或 由于复杂性的增加而不可能。这项工作的预期结果是了解如何 模块被脊髓激活，并且它们具有柔性组合的能力。这项工作将有一个 通过验证新工具和技术的实验使用，并为 以神经phip的任务依赖性方式主动激活运动模块。为此，我有 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Drexel University的神经工程计划，以提高其定量技能以更好地追求这些技能 问题。该培训计划将结合历史悠久的脊髓生物学和运动计划 在神经生物学和解剖学系内部控制正式数学的定量严格 和工程学，进一步使我能够实现这些目标，并追求成功的职业 独立研究科学家。