DEVELOPMENT AND AGING IN A VERTEBRATE AUDITORY SYSTEM

这项拟议的研究将调查听力能力的变化， 和耳朵在老化斑马鱼（Danio rerio）。 这种硬骨鱼 成为一个有用的和重要的脊椎动物模型系统的遗传 研究，它是特别感兴趣的，因为许多功能的 斑马鱼耳，包括结构和功能的感觉 受体，与哺乳动物中的受体同源。 在众多已知的 超过50种斑马鱼突变体影响耳朵作为其主要目标，而 其他的则是继发性的。 许多突变类似于 在其他脊椎动物中发现的。 斑马鱼有额外的优势， 与听力研究中最流行的遗传模型老鼠相比。 这些包括：有大量的育雏;达到性成熟， 相对年轻的年龄;具有清晰的胚胎;并且成本低， 在实验室中获取和保存。 这项研究将调查衰老神经系统的具体变化 在斑马鱼达到性成熟之前， 持续到性成熟和老年。 结果将 为理解听觉系统的变化提供基线数据 并可能提供一个模型系统， 我们可以应用已知的耳朵遗传变化来更好地了解 脊椎动物耳朵发育和衰老的方式。 这项研究将测试 斑马鱼的听觉灵敏度是否从幼年起就保持稳定 年龄，直到一段时间过去性成熟，但随后越来越穷，在老年人 动物 它还将决定感觉毛细胞的模式， 第八神经增殖后胚胎鱼。 听觉灵敏度 将使用经典的条件反射范式来确定， 成功用于其他物种。 将进行毛细胞添加 使用荧光标记和共聚焦显微镜。

The proposed study will investigate changes in the hearing capabilities and ear in aging zebrafish (Danio rerio). This teleost species has become a useful and important vertebrate model system for genetic studies, and it is of special interest since many features of the zebrafish ear, including the structure and function of the sensory receptors, are homologous to those in mammals. Among the numerous known zebrafish mutants, over 50 affect the ear as their primary target, while others affect the ear secondarily. Many of these mutations resemble those found in other vertebrates. Zebrafish have the added advantages, compared to the most popular genetic model for hearing studies, mice. These include their: having large broods; reaching sexual maturity at a relatively young age; having clear embryos; and being low cost to obtain and maintain in the laboratory. This study will investigate specific changes in the aging nervous system of zebrafish, starting before the fish reach sexual maturity and continuing through sexual maturity and into old age. The results will provide baseline data for understanding changes in the auditory system of the aging zebrafish, and potentially provide a model system in which we can apply known genetic changes in the ear to better understand the ways in which the vertebrate ear develops and ages. The study will test whether auditory sensitivity of zebrafish remains stable from a young age until a period past sexual maturity, but then get poorer in older animals. It will also determine the pattern of sensory hair cell and eighth nerve proliferation in post-embryonic fish. Auditory sensitivity will be determined using a classical conditioning paradigm that has been successfully used for other species. Hair cell addition will be done using flourescent markers and confocal microscopy.