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 脊髓似乎，至少部分地，通过结合有限数量的 刻板的“运动模块”。在运动系统中，模块结构和组合常常是功能失调的 脊髓损伤（spinal cord injury，SCI）。这项研究的长期目标是确定 运动模块结构和募集，以使人工激活或恢复，以改善适应不良 运动控制这项建议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简单脊髓中的运动池中招募运动神经元 牛蛙模型中心假设是运动模块是部分独立的， 和模式，并通过共激活的运动池依次招募特定的运动神经元。的理由 这一提议的基础是，青蛙具有独特的生理机能，允许长期生存， 脊髓上中心，允许在完整的脊髓内研究脊髓的内在能力。 肌肉组织在一个延长的时间。这一建议建立在历史研究的基础上， 模块通过电刺激或兴奋性神经递质。我将通过以下方式来检验中心假设： 两个特定目的：1）评估在脊柱状态的操作期间模块激活的独立性， （2）识别对运动模块有贡献的运动池的募集粒度。我利用 两个创新的方法来完善这些调查：1）一种新型的电极，可以记录从许多 一个新的数学工具，以确定状态依赖性之间的影响， 神经元发出连续信号，如肌肉活动。拟议的研究是重要的，因为它将 用脊髓运动模式的层次模型研究脊髓擦拭反射的桥接模块性 生成（例如运动）。对运动模块组织更精细的理解可能会澄清肌肉 以及高等物种（包括人类）中的机动车库招募，其中直接分析往往模糊不清， 由于复杂性的增加，这是不可能的。这项工作的预期成果是了解如何 模块由脊髓激活，并且它们的能力被灵活地组合。这项工作将有一个 通过验证新的工具和技术以供实验使用，进一步发挥积极影响，并为以下方面奠定基础： 在神经假体中以任务依赖的方式主动激活运动模块。为此，我 我完成了我的神经科学课程，并建议在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倡议，以提高他的定量技能，以更好地追求这些 问题.这个训练计划将联合收割机结合历史上强大的脊髓生物学和运动计划 神经生物学和解剖学系内的控制与形式数学的定量严谨 和工程，进一步装备我实现这些目标，并追求一个成功的职业生涯， 独立研究科学家。