Molecular Profiling of Song Nucleus HVC in the Zebra Finch

鸣禽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的可塑性，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鸣声控制系统的功能组织，并确定鸣声控制核中表达的基因如何促进声乐学习、大脑性别分化以及与学习相关的突触和神经元可塑性。这一目标已经大大促进了最近的玻璃斑点微阵列的可用性，其中包含约18,000个独特的脑表达cdna，这是由nads资助的研究鸣鸟神经基因组学的合作联盟产生的资源（SoNG; NS045264）。利用这一资源，我们已经确定了约200个富集于鸣叫核HVC的基因，HVC是参与鸣叫学习和产生的几个方面的关键核，并利用高通量原位杂交技术确认了其中20个基因的表达模式。我们现在建议扩展这项研究，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，以及这些细胞核中分子特化的途径。我们本提案的具体目标是：目标1：确定斑胸草雀HVC的分子特化。目的2：确定HVC分子标志物的细胞表达模式。我们提出的实验代表了建立一个明确的鸣声控制系统分子图谱和建立一个全面的、公开的斑胸草雀大脑基因表达数据库的第一步。我们期望这项研究能够发现许多特定鸣叫核的新分子标记，揭示鸣禽鸣叫控制系统的组织和功能调节机制，以及控制声乐学习的基本原理，这是人类语音和语言习得的基础。识别特定鸣叫核细胞特化的分子标记和途径，可能会揭示鸣禽鸣叫控制系统的组织和功能的调节机制，以及控制声乐学习的基本原理，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，从更广泛的意义上讲，我们的结果也可能确定大脑性别分化、学习和记忆、大脑可塑性和修复控制（包括成年期的神经元替代）的基本原理。

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.