A Gene Expression Brain Atlas of the Zebra Finch.

描述（由申请人提供）：鸣禽是神经生物学研究的主要模型，对理解人类健康和疾病问题具有广泛的意义。它们是少数进化出声音学习能力的生物之一，这种复杂的特征为人类的口语习得提供了基础。鸣禽发声的个体发生和控制鸣叫学习和产生的大脑回路组织的研究为揭示鸣叫学习的神经基础提供了独特的机会。鸣禽研究也为神经生物学中广泛的基础问题提供了新的见解，例如行为调节的基因表达，性别二态性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，以及成年期的神经发生和神经元替代。为了帮助理解鸣禽控制电路和鸣禽行为是如何被遗传机制塑造的，最近，通过美国国立卫生研究院资助的项目，鸣禽研究人员可以获得一系列广泛的现代分子和基因组资源；这些资源包括规范化的脑cDNA文库、全面的带注释的EST数据库、微阵列、BAC文库和完成的斑胸草雀基因组。这些资源在神经生物学兴趣基因和基因家族的快速鉴定、基因结构和调控域的研究、通过分子谱研究的基因调控的高通量分析以及跨主要高等脊椎动物群体的比较基因组学方面发挥了重要作用。充分利用这些基因组资源和了解基因如何与鸣禽的大脑功能和行为相关的关键下一步是在功能脑回路的背景下绘制基因表达。为了实现这一目标，我们提出了一个单一的特异性目标，即生成斑胸草雀的基因表达脑图谱。具体来说，我们建议绘制一组对鸣禽和鸟类大脑研究人员至关重要的基因（约2500个）的大脑表达图谱，并将其注册为组织学图谱，并将数据作为网络资源提供。

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.