Central Control of Motoneurons

描述：大部分的移动能力取决于脊髓和后脑的神经元网络。最近的证据表明，脊髓有一个相对简单的结构和功能组织，可以延伸到后脑。这个提议探讨了是否有一个基本的模板，神经元的组织和他们的布线在后脑，这是建立在发展过程中，并强调运动的控制。这样一个模板将提供一个概念性的组织，它将以一种重要的方式增强对大脑的一部分组织的理解，这一部分对正常运动至关重要，其正常功能在疾病和脊髓损伤后被破坏。这项工作的提出源于一项发现，即后脑神经元是根据神经递质聚集成条纹的。该提案利用了观察完整的斑马鱼幼虫大脑和脊髓的能力，以探索1）条纹是否对应于转录因子以及条纹如何发育，2）条纹内的神经元是否彼此相似，并以规则的方式投射到其他条纹中的神经元，3）条纹内神经元的电特性是否随其位置和年龄而系统地变化，从而可能导致其在正常运动期间有序激活;神经元在条纹中的位置是否反映了它被激活的运动速度。这项工作将揭示将发育与后脑神经元的后期结构和功能联系起来的基本原理。这些将告诉我们脊椎动物（包括人类）的大脑组织，并帮助我们解释和最终治疗运动障碍。运动的能力取决于位于大脑后部的神经细胞，即后脑。这个提议概述了实验，以检查后脑是如何组织控制运动。这项工作很重要，因为大脑对运动的控制在脊髓损伤和影响运动的遗传疾病中被破坏。

DESCRIPTION: Much of the ability to move depends upon networks of neurons in the spinal cord and hindbrain. Recent evidence indicates that there is a relatively simple structural and functional organization in spinal cord that may extend into the hindbrain. This proposal explores whether there is a basic template to the organization of neurons and their wiring in hindbrain that is established during development and that underlies the control of movement. Such a template would provide a conceptual organization that would enhance in a major way the understanding of the organization of a part of the brain that is critical for normal movement and whose proper function is disrupted in disease and after spinal injury. The proposed work stems from the discovery that neurons in hindbrain are clustered into stripes based on neurotransmitter. The proposal takes advantage of the ability to see into the brain and spinal cord of intact larval zebrafish to explore 1) whether the stripes correspond to transcription factors and how the stripes develop, 2) whether neurons within a stripe are similar to one another and project in a regular way to neurons in other stripes, 3) whether the electrical properties of neurons within a stripe vary systematically with their position and age in a way that might lead to their orderly activation during normal movements and 4) whether the position of a neuron in a stripe reflects the speed of the movement in which it is activated. The proposed work will reveal basic principles that link development with the later structure and function of neurons in the hindbrain. These will inform us about brain organization in vertebrates, including humans, and should help us to interpret and eventually treat movement disorders. PUBLIC HEALTH RELEVANCE The ability to move depends upon nerve cells located in the back part of the brain, the hindbrain. This proposal outlines experiments to examine how the hindbrain is organized to control movements. The work is important because the control of movement by the brain is disrupted in spinal injury as well as in genetic diseases that affect movement.