Developmental Regulation of Brain and Behavior

描述（申请人摘要）：拟定研究将阐明基因 以及它们的产物（蛋白质）对大脑的发育很重要 和行为。他们专注于结构的性别差异， 歌唱控制系统和端脑相关区域的功能 斑胸草雀只有雄性会唱歌，而控制的大脑区域和肌肉 男性的歌声比女性的大。在许多脊椎动物中， 这些类型的男性偏见的行为和形态的差异是 由性腺类固醇调节在斑胸草雀中， 但最近的数据表明，至少 前脑鸣唱控制区的分化独立于性腺分泌。 因此，将进行筛选以发现在细胞中表达的基因。 大脑发育过程中端脑的性二态模式 区域和歌唱行为。然后，调节细胞结构和/或 特定功能（例如，学习）将有针对性地进行更详细的 调查使用这种策略，女性特定的转录本， 神经钙蛋白是一种钙结合蛋白。实验将 阐明其在神经发育中的作用以及钙调节的作用。其他 研究的目标是雌激素敏感蛋白的作用， 神经营养因子（BDNF），在发展的歌曲控制核， 与它们直接相关的区域参与歌曲感知。的 脑源性神经营养因子的受体，支持神经元迁移和存活， 在这些区域，男性和女性都在学习唱歌， 雌性正在学习一首好歌的特质这些研究将阐明 学习的作用和在唱歌时活跃的大脑区域 女性的感知（男性的详细信息已经提供）， 然后将测试BDNF调节这些细胞发育的假设， 两性的端脑结构和歌曲相关功能。最后一组 许多研究探讨了调节前脑发育的机制 可能适用于运动核和发声器官肌肉，以及是否有性 分化由后脑中的性腺类固醇调节， 外围，类似于其他二态模型系统。

DESCRIPTION (applicant's abstract): The proposed studies will elucidate genes and their products (proteins) that are important for the development of brain and behavior. They focus on sexual differentiation of the structure and function of the song control system and associated regions in the telencephalon of zebra finches. Only males sing, and the brain areas and muscles that control song are larger in males than in females. In many vertebrates, the development of these types of male-biased differences in behavior and morphology is regulated by gonadal steroids. In zebra finches, some masculinization can be induced with estrogen treatment, but recent data suggest that at least the forebrain song control regions differentiate independent of gonadal secretions. Therefore, a screen will be conducted to discover genes that are expressed in a sexually dimorphic pattern in the telencephalon during development of the brain regions and singing behavior. Then, proteins regulating cytoarchitecture and/or specific functions (e.g., learning) will be targeted for more detailed investigation. Using this strategy, female-specific transcripts for neurocalcin, a calcium binding protein, were discovered. Experiments will clarify its role and that of calcium regulation in neural development. Other studies target the role of the estrogen-sensitive protein, brain derived neurotrophic factor (BDNF), in development of the song control nuclei and regions directly associated with them that are involved in song perception. The receptors for BDNF, which supports neuronal migration and survival, are present in these regions in both sexes when males are learning to sing, and perhaps females are learning the qualities of a good song. These studies will clarify the role of learning and the brain regions that are active during song perception in females (detailed information is already available for males), and will then test the hypothesis that BDNF modulates the development of these telencephalic structures and song-related functions in both sexes. The last set of studies examines whether mechanisms regulating development in the forebrain may apply to the motor nucleus and vocal organ muscles, and whether sexual differentiation is regulated by gonadal steroids in the hindbrain and periphery, similar to other dimorphic model systems.