Contribution of Motor Neurons to Fictive Motor Pattern Generation

描述（由申请人提供）：本研究的目的是阐明运动神经元在由中枢模式发生器（cpg）驱动的节律性运动模式（如呼吸或运动）的细化中的贡献。虽然CPGs的运作机制已经得到了很好的研究，但运动神经元如何将其输入转化为与行为相关的有效运动模式却知之甚少。因此，确定运动神经元是否仅仅是被动的输入输出系统，或者它们是否具有允许它们塑造运动模式的特性，这一点很重要。利用水蛭心跳中枢模式发生器作为模型系统，我将追求以下具体目标：具体目标1：表征心脏运动神经元的内在膜特性和电耦合。我将使用标准的电生理技术和染料偶联实验来表征固有的膜特性，并量化当内源性输入被阻断时与活的运动神经元的强度偶联，然后评估这些神经元假设的活动模式。具体目标3：解决我们目前的CPG控制心脏运动神经元的数学模型所假设的活动模式与生命系统中运动神经元活动模式的差异。为此，我将结合前两个目标的实验结果，对现有模型的简化模型运动神经元进行修改。总之，这些特定的目标将有助于我们理解运动神经元如何促进持续的有节奏的运动模式。此外，这里产生的见解将有助于建立一般原则，以理解中央模式生成器和负责详细阐述其输出的运动神经元之间的相互作用。脊髓损伤（SCI）的主要结果是运动控制的丧失，特别是有节奏的行为，如行走。了解功能性运动模式产生的一般原理，特别是运动神经元在形成这些模式中的作用，可能对脊髓损伤的康复策略和假肢的发展有用。

DESCRIPTION (provided by applicant): The goal of the present investigation is to elucidate the contribution of motor neurons in the elaboration of rhythmic motor patterns, such as respiration or locomotion, driven by central pattern generators (CPGs). While the mechanisms of operation of CPGs have been well investigated, less is known about how motor neurons transform their input into a behaviorally relevant fictive motor pattern. It is therefore important to determine whether motor neurons are simply passive input-output systems or whether they possess properties that allow them to shape the motor pattern. Using the leech heartbeat central pattern generator as a model system, I will pursue the following specific aims: Specific Aim 1: Characterize the intrinsic membrane properties and electrical coupling of heart motor neurons. I will use standard electrophysiological techniques and dye-coupling experiments to characterize intrinsic membrane properties and quantify the strength aoupling to living motor neurons when their endogenous input is blocked and then assess the activity patterns assumed by these neurons. Specific Aim 3: Resolve the discrepancy in activity patterns assumed by our current mathematical model of CPG control of heart motor neurons and the activity pattern of motor neurons in the living system. For this aim I will modify the simplified model motor neurons of the existing model by incorporating the experimental findings of the first two aims. Together, these specific aims will contribute to our understanding of how motor neurons contribute to ongoing rhythmic motor patterns. Furthermore, the insights generated here will help establish general principles for understanding the interplay between central pattern generators and the motor neurons responsible for elaborating their output. PUBLIC HEALTH RELEVANCE The predominant result of spinal cord injury (SCI) is the loss of motor control, particularly for rhythmic behaviors such as walking. Understanding the general principles of functional motor pattern generation and in particular the role of motor neurons in shaping these patterns may prove useful in the development of rehabilitative strategies and prostheses for SCI.