Neural Circuitry in the Developing Zebrafish Spinal Cord

斑马鱼脊髓发育中的神经回路

• 批准号: 6854786
• 负责人: MARK M VOIGT
• 金额: $ 7.35万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6854786
• 关键词: developmental genetics; developmental neurobiology; genetic markers; genetic screening; genetically modified animals; intercellular connection; neural information processing; neuroanatomy; neurochemistry; reporter genes; spinal cord; vertebrate embryology; zebrafish

DESCRIPTION (provided by applicant): A zebrafish embryo goes from a single-cell to an organism with a functioning nervous system within its first 24 hours of existence. By 24 hours post-fertilization, the embryo has mechanosensory-mediated reflex motor behaviors and by 96 hr the fish is a free-swimming larva. The manifestation of these behaviors is due to the establishment of a simple but effective neural network in the spinal cord and hindbrain of the developing fish. This simple nervous system provides the scaffolding for further expansion during maturation of the organism. Elucidating the mechanisms underlying early nervous system formation in the zebrafish could have a huge impact on our understanding of how many neurological disorders arise in man. The properties of the embryonic/larval zebrafish has made it uniquely suited to study the formation of a neural network- it's fertilized externally, transparent during its development and lends itself easily to molecular techniques such as anti-sense treatment and transgenesis. Anatomical studies using dye labeling have yielded information regarding the morphologies of spinal neurons during these early time points, suggesting the presence of some 11-15 neurons per hemi-segment of the cord between 24-96 HPF. In addition, these studies have provided some insight into how the neurons connect to one another to form a network. However, almost nothing is known about how these neurons communicate amongst each other. It is the purpose of this proposal to generate transgenic fish lines that will enable the elucidation of the neurochemical anatomy of the developing spinal cord. Not only will these fish provide information as to the connectivity of the various spinal and supraspinal pathways, but they will also provide markers for use in functional studies utilizing either co-expression (e.g., with calcium indicators) or electrophysiological approaches. In addition, they can provide markers for specific neuronal types that can be used in forward genetic screens aimed at identifying genes required for either phenotype or connectivity decisions in these cells

描述（由申请人提供）：斑马鱼胚胎从单细胞到生物体，在其存在的前24小时内具有正常的神经系统。在施肥后24小时内，胚胎具有机械介导的反射运动行为，到96小时，鱼是一个自由速度的幼虫。这些行为的表现是由于在发育中的鱼的脊髓和后脑中建立了一个简单但有效的神经网络。这种简单的神经系统为生物体成熟过程提供了进一步扩张的脚手架。阐明斑马鱼早期神经系统形成的机制可能会对我们对人中有多少神经系统疾病的理解产生巨大影响。胚胎/幼虫斑马鱼的特性使其非常适合研究神经网络的形成 - 它在其发育过程中是在外部受精，透明的，并且很容易借给分子技术，例如抗敏感治疗和转变。使用染料标记的解剖学研究产生了有关这些早期时间点脊柱神经元形态的信息，这表明每个半段在24-96 hpf之间存在约11-15个神经元。此外，这些研究还深入了解了神经元如何相互连接以形成网络。但是，这些神经元如何相互交流几乎一无所知。该提案的目的是产生转基因鱼类线，以阐明发育中的脊髓神经化学解剖结构。这些鱼类不仅会提供有关各种脊柱和脊柱上途径的连通性的信息，而且还将提供用于利用共表达（例如，使用钙指标）或电生理方法的功能研究中使用的标记。此外，它们可以为特定的神经元类型提供标记，这些类型可用于远期遗传筛选，旨在识别这些细胞中表型或连通性决策所需的基因