Central Control of Motoneurons

描述：运动的能力很大程度上依赖于脊髓和后脑的神经元网络。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，可以延伸到后脑。这一建议探索了后脑中神经元的组织及其连接是否存在一个基本模板，该模板是在发育过程中建立的，是控制运动的基础。这样的模板将提供一个概念性的组织，它将在很大程度上加强对大脑某一部分的组织的理解，该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受到干扰。这项拟议的工作源于一项发现，即根据神经递质，后脑中的神经元聚集成条纹。该方案利用完整斑马鱼幼体对大脑和脊髓的观察能力，探索1)条纹是否与转录因子对应，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因其位置和年龄而有系统地变化，从而可能导致它们在正常运动中有序激活；4)神经元在条纹中的位置是否反映了它被激活的运动速度。这项拟议的工作将揭示将发育与后脑神经元后来的结构和功能联系起来的基本原理。这些将让我们了解包括人类在内的脊椎动物的大脑组织，应该有助于我们解释并最终治疗运动障碍。公共卫生相关性运动能力取决于位于大脑后部的神经细胞，即后脑。这项提议概述了检验后脑是如何组织起来控制运动的实验。这项工作很重要，因为在脊椎损伤和影响运动的遗传病中，大脑对运动的控制被破坏。

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.