Central Control of Motoneurons

描述：运动能力很大程度上依赖于脊髓和后脑中的神经元网络。最近的证据表明，脊髓中有一个相对简单的结构和功能组织，可能延伸到后脑。这一提议探讨了在发育过程中是否存在一个神经元组织及其在后脑中的连接的基本模板，并奠定了运动控制的基础。这样一个模板将提供一个概念性的组织，它将以一种主要的方式加强对大脑中对正常运动至关重要的部分的组织的理解，它的正常功能在疾病和脊髓损伤后被破坏。这项提议的工作源于后脑的神经元根据神经递质聚集成条纹的发现。该提案利用观察完整斑马鱼幼虫的大脑和脊髓的能力来探索1)条纹是否与转录因子相对应以及条纹是如何发育的；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着它们的位置和年龄系统性地变化，从而可能导致它们在正常运动中有序地激活；4)条纹内神经元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。这些将告诉我们关于脊椎动物的大脑组织，包括人类，并应该帮助我们解释和最终治疗运动障碍。与公共卫生相关的活动能力取决于位于大脑后部的神经细胞，即后脑。这个提议概述了研究后脑是如何组织起来控制运动的实验。这项工作很重要，因为在脊髓损伤和影响运动的遗传疾病中，大脑对运动的控制被破坏了。

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.