Neural Circuitry in the Developing Zebrafish Spinal Cord

斑马鱼脊髓发育中的神经回路

• 批准号: 6947270
• 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 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6947270
• 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）：斑马鱼胚胎在其存在的最初 24 小时内从单细胞转变为具有神经系统功能的生物体。受精后 24 小时，胚胎具有机械感觉介导的反射运动行为，到 96 小时，鱼就成为自由游动的幼虫。这些行为的表现是由于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中的进一步扩展提供了支架。阐明斑马鱼早期神经系统形成的机制可能会对我们了解人类出现多少种神经系统疾病产生巨大影响。斑马鱼胚胎/幼虫的特性使其特别适合研究神经网络的形成——它在体外受精，在发育过程中是透明的，并且很容易采用反义处理和转基因等分子技术。使用染料标记的解剖学研究已经获得了有关这些早期时间点脊髓神经元形态的信息，表明在 24-96 HPF 之间，脊髓的每个半段存在约 11-15 个神经元。此外，这些研究还为神经元如何相互连接形成网络提供了一些见解。然而，人们对这些神经元如何相互通信几乎一无所知。该提案的目的是产生转基因鱼系，以阐明发育中脊髓的神经化学解剖结构。这些鱼不仅将提供有关各种脊髓和脊髓上通路的连接性的信息，而且还将提供用于利用共表达（例如，与钙指示剂）或电生理学方法的功能研究的标记。此外，它们还可以提供特定神经元类型的标记，这些标记可用于正向遗传筛选，旨在识别这些细胞中表型或连接决策所需的基因