Probing the origin and function of a novel subset of motor neurons

探索运动神经元新亚群的起源和功能

• 批准号: 9317614
• 负责人: Helen Lai
• 金额: $ 24.3万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317614
• 关键词: Address; Affect; Amyotrophic Lateral Sclerosis; Animals; Atrophic; Axon; Back; Cells; Cerebellum; Computer Simulation; Contralateral; Data; Degenerative Disorder; Development; Dorsal; Electrophysiology (science); Embryonic Development; Foundations; Genetic; Genetic Techniques; Goals; Label; Learning; Lumbar spinal cord structure; Modeling; Monkeys; Morphology; Motion; Motor; Motor Neuron Disease; Motor Neurons; Motor Skills; Motor output; Movement; Mus; Muscle; Nature; Neurodegenerative Disorders; Neurons; Neurosciences; Perception; Phenotype; Physiological; Play; Prosthesis; Research; Robotics; Role; Sensory; Source; Spinal; Spinal Cord; Spinal cord injury; System; Techniques; Testing; Theoretical model; Travel; Viral; base; design; experimental study; follow-up; genetic manipulation; insight; molecular marker; motor control; motor learning; motor neuron degeneration; motor neuron development; novel; optogenetics; progenitor; programs; sensory input; success; transcription factor

Project Summary/Abstract: A fundamental question in vertebrate motion is how proper controlled motor output is achieved. A major concept in neuroscience that helps to explain controlled movement is the idea of corollary discharge. This idea asserts that copies of outgoing motor commands are sent back to the motor system and compared to actual sensory information to distinguish self-generated movements from externally-generated ones. In this way, smooth and corrective movements can be executed based on how predicted internal models of motor action match sensory input. While there is electrophysiological evidence for corollary discharge in several motor circuits, the neuroanatomical underpinnings of this physiological phenomenon is less well-described. In particular, neurons that have been identified as sources of corollary discharge to the cerebellum, a major integration and motor learning center, has been limited to regions rostral of the spinal cord. Preliminary data suggests that a subset of motor neurons in the spinal cord is derived from a novel progenitor domain that can project axon collaterals to both muscle and the cerebellum in mice. The goal of this proposal will be to examine the developmental origins and axonal projections of this motor neuron subset. The first aim will identify the functional motor pools, subtype, and development of the motor neurons demarcated by this novel motor neuron subset using a variety of genetic techniques combined with molecular marker analyses. The second aim will use a range of genetic, neuronal tracing, and optogenetic techniques to address whether motor neurons in the spinal cord, in particular those marked by this novel motor neuron subset, are sending axon collaterals to both muscle and the cerebellum. Confirmation of this second aim will provide a neuroanatomical basis for corollary discharge to the cerebellum from motor neurons. Altogether, the objective of this project is to understand the development and connectivity of a novel subset of motor neurons that may be communicating internal copies of motor commands for smooth motor output. Success in these aims will lay the foundation for a research program exploring the function and utility of these motor neurons in achieving proper motor control. Discovery of the circuits underlying controlled movement will help to refine computational models of motor execution and learning that could influence the fields of prosthetics and robotics. In addition, recognizing how motor circuits are wired and function in endogenous contexts will influence our understanding of the motor mechanisms damaged during spinal cord injury and neurodegenerative disease. In particular, research into how corollary discharge from these motor neurons is affected in amyotrophic lateral sclerosis or spinal motor atrophy models could provide new insights into the progression and phenotype of these motor neuron diseases.

项目概要/摘要： 脊椎动物运动中的一个基本问题是如何实现适当的受控运动输出。一个主要 在神经科学中，有一个概念有助于解释受控运动，那就是必然放电的概念。这个想法 断言输出电机命令的副本被发送回电机系统，并与实际电机命令进行比较。 感觉信息来区分自我产生的运动和外部产生的运动。通过这种方式， 可以基于运动动作的预测内部模型如何 匹配感官输入虽然有电生理学证据表明，在一些运动神经元中， 由于神经回路的存在，这种生理现象的神经解剖学基础还没有得到很好的描述。在 特别是，神经元已被确定为小脑的必然放电来源，这是一个主要的 整合和运动学习中心，一直局限于脊髓的喙部区域。 初步数据表明，脊髓中的一个运动神经元子集来自一种新的 在小鼠中，它可以将轴突侧支投射到肌肉和小脑。这个目标 我们的建议将是检查这个运动神经元亚群的发育起源和轴突投射。的 第一个目标是确定功能性运动池、亚型和运动神经元的发育， 这种新的运动神经元亚群使用多种遗传技术结合分子标记， 分析。第二个目标将使用一系列遗传，神经元追踪和光遗传学技术来解决 脊髓中的运动神经元，特别是由这种新的运动神经元亚群标记的运动神经元， 将轴突侧支输送到肌肉和小脑。第二个目标的确认将提供一个 运动神经元向小脑的必然放电的神经解剖学基础。 总而言之，这个项目的目标是了解一部小说的发展和联系 运动神经元的一个子集，可能正在传递运动命令的内部副本，以实现平滑运动 输出.这些目标的成功将为研究计划探索的功能和效用奠定基础， 这些运动神经元实现适当的运动控制。发现了控制性的潜在电路 运动将有助于完善运动执行和学习的计算模型，这些模型可能会影响运动员的运动能力。 假肢和机器人领域。此外，认识到运动电路是如何连接和功能， 内源性背景将影响我们对脊髓损伤过程中运动机制的理解， 损伤和神经变性疾病。特别是，研究这些运动员的伴随放电， 神经元在肌萎缩侧索硬化或脊髓运动萎缩模型中受到影响， 这些运动神经元疾病的进展和表型。