Developmental Regulation of Brain and Behavior

描述(申请人摘要)：拟议的研究将阐明基因 以及它们对大脑发育至关重要的产物(蛋白质) 和行为。他们关注的是结构的性别分化和 端脑中歌唱控制系统及其相关区域的功能 斑马雀。只有男性唱歌，控制大脑区域和肌肉的 男性的歌声比女性的要大。在许多脊椎动物中，发育 在这些类型的男性偏见的行为和形态差异中， 由性腺类固醇调节。在斑马雀身上，一些雄性化可以 用雌激素治疗诱导，但最近的数据表明，至少 前脑歌曲控制区的分化与性腺分泌物无关。 因此，将进行一项筛选，以发现在 大脑发育过程中端脑的性二态模式 地域和歌唱行为。然后，调节细胞结构和/或 具体功能(例如，学习)将针对更详细的内容 调查。使用这一策略，女性特有的文字记录 神经钙素是一种钙结合蛋白。实验将会 阐明它的作用和钙调节在神经发育中的作用。其他 研究的目标是雌激素敏感蛋白的作用，脑源性 神经营养因子(BDNF)在SONG控制核团发育中的作用 与他们直接相关的参与歌曲感知的区域。这个 脑源性神经营养因子的受体存在，它支持神经元的迁移和存活 在这些区域，无论男女，当男性学习唱歌时，也许 女性正在学习一首好歌的品质。这些研究将澄清 学习的作用和歌唱时活跃的大脑区域 女性的感知(男性已经有了详细的信息)， 然后将检验BDNF调节这些细胞的发育的假设 两性端脑结构和歌唱相关功能。最后一套 的研究检查了调节前脑发育的机制 可适用于运动核和发声器官的肌肉，且是否有性 分化是由后脑中的性腺类固醇和 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.