Collaborative Research: Role of Neurofilament Transport in the Growth of Axonal Caliber

合作研究：神经丝运输在轴突口径增长中的作用

• 批准号: 0818412
• 负责人: Peter Jung
• 金额: $ 13.35万
• 依托单位: Ohio University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0818412&HistoricalAwards=false
• 关键词: Collaborative; Research; Role; Neurofilament; Transport

Nerve cells communicate by conducting electrical signals along slender cytoplasmic extensions known as axons. Animals have evolved two basic mechanisms for increasing axonal conduction velocity. One is to increase axonal diameter and the other is to insulate axons by a process called myelination, which is a tight spiral wrapping of the axons that is formed by myelinating cells. In vertebrates the growth of axon diameter is caused principally by the accumulation of space-filling cytoskeletal polymers called neurofilaments inside the axons, and this is regulated locally by chemical signals from the myelinating cells. It is known that neurofilaments are transported along axons and that they alternate between rapid movements and prolonged pauses. The proportion of the time that the neurofilaments spend pausing is likely to be a principal determinant of their residence time in axons. This is a collaborative experimental and modeling project involving a biologist at Ohio State University and a physicist at Ohio University. The central hypothesis to be tested is that myelinating cells control axonal caliber by regulating neurofilament pausing. A computational model will be developed that relates the moving and pausing behavior of neurofilaments to their distribution along axons. The model will be based on detailed kinetic parameters of neurofilament movement derived experimentally in cultured neurons and will be verified experimentally by fluorescence microscopy of neurofilament movement in myelinated axons in tissue culture. The proposed research will generate a rigorous and quantitative framework that relates the size and shape of axons, which is a key influence on their electrical properties, to the moving and pausing behavior of their internal constituents. The research will involve graduate and undergraduate students in both the physical and biological sciences, providing an integrated and cross-disciplinary training experience at the interface between computational and experimental biology.

神经细胞通过沿着细长的细胞质延伸（称为轴突）传导电信号来进行通信。动物已经进化出两种增加轴突传导速度的基本机制。一种是增加轴突直径，另一种是通过称为髓鞘形成的过程来隔离轴突，髓鞘形成是由髓鞘细胞形成的轴突的紧密螺旋包裹。在脊椎动物中，轴突直径的增长主要是由轴突内称为神经丝的充满空间的细胞骨架聚合物的积累引起的，并且这受到来自髓鞘细胞的化学信号的局部调节。众所周知，神经丝沿着轴突运输，并且它们在快速运动和长时间停顿之间交替。神经丝暂停的时间比例可能是其在轴突中停留时间的主要决定因素。这是一个合作实验和建模项目，涉及俄亥俄州立大学的生物学家和俄亥俄大学的物理学家。要测试的中心假设是髓鞘细胞通过调节神经丝暂停来控制轴突口径。将开发一个计算模型，将神经丝的移动和暂停行为与其沿轴突的分布联系起来。该模型将基于在培养神经元中通过实验得出的神经丝运动的详细动力学参数，并将通过组织培养中有髓轴突中神经丝运动的荧光显微镜进行实验验证。拟议的研究将产生一个严格的定量框架，将轴突的大小和形状与其内部成分的移动和暂停行为联系起来，轴突的大小和形状是对其电特性的关键影响。该研究将涉及物理科学和生物科学领域的研究生和本科生，在计算生物学和实验生物学之间的界面提供综合和跨学科的培训经验。