A Gene Expression Brain Atlas of the Zebra Finch.

描述(由申请者提供)：鸣禽是神经生物学研究的领先模型，对理解人类健康和疾病问题具有广泛的影响。它们是少数几个进化了发声学习的生物之一，这是一种复杂的特征，为人类获得口语提供了基础。对鸣禽发声的个体发育和控制歌曲学习和产生的大脑回路的组织的研究为揭示发声学习的神经基础提供了独特的机会。鸣鸟的研究还为神经生物学中的一系列基本问题提供了新的见解，如行为调控的基因表达、性二态和性类固醇对大脑结构和功能的影响、光周期和季节性大脑可塑性的调节、睡眠在学习中的作用、生殖和社会行为的神经内分泌调节，以及成年后的神经发生和神经元替换。为了帮助理解鸣叫控制回路和鸟鸣行为是如何由遗传机制塑造的，最近通过美国国立卫生研究院资助的计划，鸣鸟研究人员可以获得一系列现代分子和基因组资源；这些资源包括标准化的脑cDNA文库、全面的注释EST数据库、微阵列、BAC文库和完整的斑马雀基因组。这些资源有助于快速鉴定具有神经生物学意义的基因和基因家族，研究基因结构和调节域，通过分子图谱研究高通量分析基因调控，以及主要高等脊椎动物群体的比较基因组学。要充分利用这些基因组资源并了解基因如何与鸣禽的大脑功能和行为相关，下一步的关键是在大脑功能回路的背景下绘制基因表达图。为了实现这一目标，我们提出了一个单一的特定目标，即生成斑马雀的基因表达脑图谱。具体地说，我们建议绘制一大组对鸣禽和鸟类大脑研究人员至关重要的基因(~2,500)的大脑表达图，注册到组织学图谱，并将数据作为基于网络的资源提供。 公共卫生相关性：该资源将对进一步建立鸣禽作为神经生物学研究的主要模式生物产生巨大影响，并证实它们与人类健康和疾病的相关性，特别是言语和语言学习和损伤的神经基础。它将提供一个极大地改善斑雀大脑的分子特征，允许神经递质和受体的歌曲核团的轮廓，并揭示Aene调节MAV如何与SONA系统联系在一起。歌唱行为与声乐学习。

DESCRIPTION (provided by applicant): Songbirds are a leading model of neurobiological research with wide implications for understanding issues of human health and disease. They are among the few organisms that have evolved vocal learning, a complex trait that provides the basis of spoken language acquisition in humans. Studies of the ontogeny of songbird vocalizations and the organization of the brain circuitry that controls song learning and production have provided unique opportunities for uncovering the neural bases of vocal learning. Songbird research has also contributed novel insights into a broad range of fundamental questions in neurobiology, such as behaviorally- regulated gene expression, sex dimorphisms and the effects of sex steroids on brain structure and function, photoperiodicity and the regulation of seasonal brain plasticity, the role of sleep in learning, the neuroendocrine regulation of reproductive and social behaviors, and neurogenesis and neuronal replacement in adulthood. To help understand how the song control circuitry and birdsong behavior are shaped by genetic mechanisms, a wide set of modern molecular and genomic resources have recently become available to songbird researchers through NIH-funded initiatives; such resources include normalized brain cDNA libraries, comprehensive annotated EST databases, microarrays, a BAC library and the completed the zebra finch genome. Such resources have been instrumental in the rapid identification of genes and gene families of neurobiological interest, the study of gene structure and regulatory domains, high- throughput analysis of gene regulation through molecular profiling studies, and comparative genomics across the major higher vertebrate groups. A key next step in making full use of these genomic resources and understanding how genes relate to brain function and behavior in songbirds is to map gene expression in the context of functional brain circuits. To achieve this goal, we propose a single Specific Aim, namely to generate a Gene Expression Brain Atlas of the Zebra Finch. Specifically we propose to map the brain expression of a large set of genes (~2,500) that are of key importance to songbird and avian brain researchers, in register with a histological atlas, and make the data available as a web-based resource. PUBLIC HEALTH RELEVANCE: This resource will have an enormous impact on further establishing songbirds as a major model organism for neurobiological research, and substantiating their relevance for human health and disease, in particular the neural basis of speech and language learning and impairment. It will provide a vastly improved molecular characterization of the zebra finch brain, allow for neurotransmitter and receptor profiling of song nuclei, and reveal how aene regulation mav be linked to the sona svstem. singing behavior and vocal learning.