Molecular Profiling of Song Nucleus HVC in the Zebra Finch

描述(申请人提供)：对鸣禽的鸣叫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，包括发声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的可塑性，以及脊椎动物大脑中神经元持续替代的发现。我们的长期目标是了解歌曲控制系统的功能组织，并确定歌曲控制核团中表达的基因如何对发声学习、大脑性别分化以及与学习相关的突触和神经元可塑性做出贡献。最近，玻璃斑点微阵列的出现极大地促进了这一目标的实现，该微阵列包含约18,000个独特的大脑表达的cDNA，这是由NINDS资助的研究鸣禽神经基因组学的合作联盟产生的资源(SONG；NS045264)。利用这个资源，我们已经鉴定了大约200个富含在歌曲学习和产生的关键核团HVC中的基因，并利用高通量原位杂交技术确定了其中20个基因的表达模式。我们现在建议扩展这项研究，并对HVC和鸣禽大脑中表达的基因进行全面的区域和细胞分析，以及这些核内潜在的分子专门化的途径。我们对这项建议的具体目标是：目标1：确定斑雀体内HVC的分子专化性。目的2：确定HVC分子标志物的细胞表达模式。我们提出的实验是为斑马雀大脑生成一个明确的鸣声控制系统的分子图谱和建立一个全面的、公开可用的基因表达数据库的第一步。我们预计，这项研究将发现许多新的特定歌唱核团的分子标记，并揭示参与调节鸣禽歌唱控制系统的组织和功能的机制，以及控制发声学习的基本原则，这是人类言语和语言习得的基础。公共卫生相关性识别特定鸣禽核团细胞特化的分子标记和途径，可能会揭示调节鸣禽鸣叫控制系统的组织和功能的机制，以及控制发声学习的基本原则，这是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，在更广泛的意义上，我们的结果也可能确定大脑性别分化、学习和记忆的基本原理，以及大脑可塑性和修复的控制，包括成年后的神经元替换。

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.