STEROID CONTROL OF SEX DIFFERENCES IN BRAIN AND BEHAVIOR

这项建议旨在建立神经网站和细胞机制 性腺激素通过这种方式促进发声能力的性别差异， 雀形目鸟类的神经组织 在斑胸草雀中，鸣叫是一种 雄激素依赖的行为，通常只由男性产生。 雌激素在发育过程中起作用，决定组织， 重要的是，雄激素在鸣唱区域内的积累程度。 雄激素在成年期诱导进一步的神经生长， 发展 该提案侧重于三个重要问题 歌曲系统的性别差异。 第一个问题是， 雌激素（E2）的作用是使发展中地区男性化。 类固醇 放射自显影术将用于评估哪个发育中的宋区 积累E2。 颅内E2植入物将用于确定 这些神经部位是E2作用的主要靶点， 间接地或跨突触地影响。 第二个问题涉及 早期E2暴露如何决定雄激素积累的程度， 成人大脑的敏感性。 类固醇放射自显影将用于 评估雄激素在发育中的鸣唱区域内的积累，因此， E2是否诱导或保持雄性激素的阳性模式 积累 E2这方面存在一个关键时期 将通过检查雄激素蓄积的模式来确定作用 在成年期给予全身性E2的鸟类中。 胸苷放射自显影将 用于确定神经发生是否发生在E2的关键时期 作用，如果E2刺激这种神经发生。 第三个问题是关于 雄激素作用的神经部位和功能意义 成人大脑 利用光学显微镜分析细胞形态， 区域和行为分析，雄激素诱导的神经元的时间进程， 变化将被评估并与发声发展相关。 预测 雄激素积累细胞将建立在同时 使用荧光逆行示踪剂和类固醇放射自显影，以及 颅内抗雄激素植入物将用于确定 某些鸣唱区域的雄激素积聚神经元 雄激素诱导的神经生长在他们的传出目标。 更好的 了解性分化的细胞机制 性功能异常治疗的巨大希望 人类的分化。 这也将增加我们对 细胞机制，允许神经可塑性的方面， 在鸟类中表现出来，但在人类中却不那么强烈。

This proposal is aimed at establishing neural sites and cellular mechanisms by which gonadal hormones promote sex differences in vocal ability and neural organization in passerine birds. In zebra finches, song is an androgen-dependent behavior that is normally produced only by males. Estrogens act during development to determine the organization, and, importantly, the extent androgen accumulation within song regions. Androgens induce further neural growth in adulthood, and promote song development. This proposal focuses on three important issues regarding the secual differentiation of the song system. The first regards where estrogen (E2) acts to masculinize developing regions. Steroid autoradiography will be used to assess which developing song region accumulate E2. Intracranial E2 implants will be used to determine which of these neural sites are primary targets for E2 action, and which are influenced indirectly, or trans-synaptically. The second issue concerns how early E2 exposure determines the extent of androgen accumulation and sensitivity in the adult brain. Steroid autoradiography will be used to assess androgen accumulation within developing song regions and hence, whether E2 induces, or preserves a masculine pattern of androgen accumulation. The existence of a critical period for this aspect of E2 action will be determine by examining the pattern of androgen accumulation in birds given systemic E2 in adulthood. Thymidine autoradiography will be used to determine if neurogenesis occurs during the critical period of E2 action, and if E2 stimulates this neurogenesis. The third issue regards the neural sites and functional significance of androgen action in the adult brain. Using light microscopic analyses of cell morphology in song regions, and behavioral analyses, the timecourse of androgen-induced neural change will be assessed and related to vocal development. Projections of androgen-accumulating cells will be established throught the simultaneous use of fluorescent retrograde tracers and steroid autoradiography, and intracranial antiandrogen implants will be used to determine if androgen-accumulating neurons in certain song regions mediate androgen-induced neural growth in their efferent targets. A better understanding of the cellular mechanisms of sexual differentiation hold great promise for therapeutic remedy of abnormalities in sexual differentiation in humans. It will also increase our understanding of cellular mechanisms that permit aspects of neural plasticity that are manifest in birds, yet less robust in humans.