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

研究摘要 脊髓似乎，至少部分地，通过结合有限数量的 千篇一律的‘马达模块’。在电机系统中，模块结构和组合经常出现功能障碍 疾病，如脊髓损伤(SCI)。这项研究的长期目标是确定 运动模块结构和招募，以实现人工激活或修复，以改善适应不良 马达控制。这项建议的目的是确定脊髓运动模块是如何在 以及这些模块如何从较简单的脊髓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，产生两种节律 和模式，并在共同激活的运动池中轮流招募特定的运动神经元。其基本原理是 这一建议的基础是，青蛙有独特的生理能力，即使破坏了 脊柱上中枢，使脊髓的内在能力能够在完整的 在很长一段时间内肌肉发达。这项建议建立在历史研究的基础上，它激活了马达 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 两个特定的目的：1)评估在脊髓状态操作过程中模块激活的独立性， 以及2)辨别对运动模块有贡献的运动池的招募粒度。我利用 两种创新的方法来完善这些研究：1)一种新型的电极，可以从许多记录 同时使用单个电机单元和2)一种新的数学工具，用于识别 具有连续信号的尖峰神经元，如肌肉活动。这项拟议的研究具有重大意义，因为它将 脊髓运动模式分层模型在脊髓擦拭反射中的桥式模块化研究 生成(例如，移动)。对运动模块组织有更深入的了解可能会使肌肉更加清晰 以及在包括人类在内的高等物种中招募运动池，在这些物种中，直接分析通常是模糊的或 由于复杂性增加，这是不可能的。这项工作的预期结果是理解如何 模块由脊髓激活，它们的能力可以灵活地组合起来。这部作品将会有一个 通过验证用于实验使用的新工具和技术进一步产生积极影响，并为 在神经假体中，以任务依赖的方式主动激活运动模块。为此，我已经 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增加他的量化技能，以更好地追求这些 问题。这项训练计划将把历史悠久的脊髓生物学和运动训练结合起来 神经生物学和解剖学系的控制与形式数学的定量严谨性 和工程学，进一步装备我实现这些目标并追求成功的职业生涯 独立研究科学家。

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.