Transgenic Zebra Finches: New Tool for Studying Learning and Brain Repair.

描述(申请人提供)：这里提出的工作是为了建立一种高效的生产转基因斑马雀的程序而设计的。斑马雀是一种鸣禽，它们通过模仿成年鸟的歌声来学习歌唱。调节这种行为的大脑区域是高度模块化的，在解剖学上有很好的定义；它们统称为“歌唱系统”。在这个系统中，编码歌曲的关键神经元群体在成年后不断被替换。解剖学和行为之间的紧密关系，加上罕见的持续替换产生行为的细胞的能力，使SONG系统成为研究学习和神经元替换的基本生物学的一个非常有吸引力的模型。几个关键资源已经和目前正在产生，以促进在更简约的水平上对该系统的研究：该物种的基因组已经测序，已经生成、测序和出版了cDNA文库，并且已经创建并提供了一个BAC文库。这些资源有可能帮助阐明调节歌曲行为的分子机制和细胞属性。然而，为了充分利用这些资源，必须有可能在体内操纵基因表达，而我们目前还不能在斑马雀身上做到这一点。在过去的一年里，这个实验室将其资源投入到开发这样一个工具上，我们所采用的方法使我们能够克服关键障碍并取得重大进展。这里概述了这一进展，以及我们将采取的步骤，以制定一种有效的协议来制造转基因鸣禽。 公共卫生相关性：成年斑马雀的神经发生和神经元替换发生在歌唱学习的背景下。本项目是关于转基因斑马雀的生产，将有助于我们了解成年脑内神经元替代的机制、功能和治疗潜力。

DESCRIPTION (provided by applicant): The work proposed here is designed to build on what we have accomplished thus far toward establishing an efficient procedure for producing transgenic zebra finches. Zebra finches are songbirds that learn their song by imitating that of an adult. The brain regions that mediate this behavior are highly modular and well defined anatomically; they are collectively referred to as the "song system". Within this system a key population of neurons encoding the song is replaced continuously in adulthood. The tight relationship between anatomy and behavior, together with the rare ability to continuously replace those cells that produce the behavior, have made the song system a very attractive model for studying the basic biology of learning and neuronal replacement. Several key resources have been and are presently being generated to facilitate the study of this system at ever more reductionistic levels: the genome of this species has been sequenced, cDNA libraries have been generated, sequenced and published, and a BAC library has been created and made available. These resources have the potential to help elucidate the molecular mechanisms and cellular properties that mediate song behavior. However, to take full advantage of these resources it has to be possible to manipulate gene expression in vivo, which we cannot yet do in zebra finches. Over the last year this laboratory has devoted its resources to the development of such a tool, and the methods we have employed have allowed us to overcome key obstacles and make significant progress. That progress is outlined here as well as the steps we will take to produce an efficient protocol for making transgenic songbirds. PUBLIC HEALTH RELEVANCE: Neurogenesis and neuronal replacement occur in the context of song learning in adult zebra finches. This project is about the production of transgenic zebra finches that will help us understand the mechanisms, function and therapeutic potential of neuronal replacement in adult brain.