Molecular Profiling of Song Nucleus HVC in the Zebra Finch

描述（由申请人提供）：鸣禽鸣唱控制系统的研究为神经生物学的基本问题提供了基本的见解，包括声音学习和交流的神经元基础，性激素对大脑和行为的作用，季节性和成年神经元可塑性，以及脊椎动物大脑中持续神经元替代的发现。我们的长期目标是了解歌曲控制系统的功能组织，并确定在歌曲控制核中表达的基因如何有助于发声学习，大脑性别分化以及学习相关的突触和神经元可塑性。这一目标已经大大促进了最近可用的玻璃斑点微阵列含有~ 18，000独特的脑表达的cDNA，由NINDS资助的合作财团研究鸣禽神经基因组学（SoNG; NS 045264）产生的资源。利用这一资源，我们已经确定了约200个基因，丰富的歌曲核HVC，一个关键的核参与几个方面的歌曲学习和生产，并确认了20这些使用高通量原位杂交技术的表达模式。我们现在建议扩展这项研究，并提供一个全面的区域和细胞分析的基因表达在HVC和鸣禽大脑一般，和这些细胞核内的分子特化的途径。我们的具体目标是这个建议：目标1：确定分子特化的HVC在斑胸草雀。目的2：探讨肝细胞癌分子标志物的细胞表达模式。我们提出的实验代表了第一步，产生一个明确的分子分析的鸣禽的歌曲控制系统，并建立一个全面的，公开的基因表达数据库斑胸草雀大脑。我们预计，这项研究将确定许多新的分子标记的特定的歌曲核和揭示机制参与调节鸣禽的歌曲控制系统的组织和功能，以及控制声乐学习的基本原则，语音和语言习得的基础在人类。公共卫生相关性识别特定鸣禽细胞核的细胞特化的分子标记物和途径可能会揭示鸣禽控制系统的组织和功能的调节机制，以及控制发声学习的基本原则，人类言语和语言习得的基础。因此，我们的研究可能有助于阐明言语和语言障碍的基本机制。然而，从更广泛的意义上说，我们的研究结果也可能确定大脑性别分化，学习和记忆以及大脑可塑性和修复控制的基本原则，包括成年期的神经元替代。

DESCRIPTION (provided by applicant): The study of the song control system of songbirds has provided fundamental insights into basic questions in neurobiology, including the neuronal basis of vocal learning and communication, the action of sex hormones on the brain and behavior, seasonal and adult neuronal plasticity, and the discovery of continued neuronal replacement in the vertebrate brain. Our long-term goal is to understand the functional organization of the song control system, and to determine how genes expressed in song control nuclei contribute to vocal learning, brain sex differentiation, and learning-related synaptic and neuronal plasticity. This goal has been greatly facilitated by the recent availability of glass-spotted microarrays containing ~18,000 unique brain-expressed cDNAs, a resource generated by an NINDS-funded collaborative consortium to study songbird neurogenomics (SoNG; NS045264). Using this resource, we have already identified ~200 genes that are enriched in the song nucleus HVC, a key nucleus involved in several aspects of song learning and production, and confirmed the patterns of expression for 20 of these using high-throughput in situ hybridization techniques. We now propose to extend this study and provide a comprehensive regional and cellular analysis of genes expressed in HVC and the songbird brain in general, and the pathways underlying molecular specializations within these nuclei. Our Specific Aims for this proposal are to: Aim 1: To identify molecular specializations of HVC in zebra finches. Aim 2: To determine the cellular expression patterns of molecular markers of HVC. Our proposed experiments represent the first steps towards generating a definitive molecular profiling of the oscine song control system and building a comprehensive, publicly available gene expression database for the zebra finch brain. We anticipate that this study will identify many novel molecular markers of specific song nuclei and uncover mechanisms involved in regulating the organization and function of the song control system of songbirds, and basic principles that control vocal learning, the basis for speech and language acquisition in humans. PUBLIC HEALTH RELEVANCE The identification of molecular markers and pathways underlying cellular specializations of specific song nuclei will likely uncover mechanisms that regulate the organization and function of the song control system of songbirds, and basic principles that control vocal learning, the basis for speech and language acquisition in humans. Our research may therefore help elucidate basic mechanisms of speech and language disorders. In a broader sense, however, our results are also likely to identify basic principles underlying brain sexual differentiation, learning and memory, and the control of brain plasticity and repair, including neuronal replacement during adulthood.