STEROID CONTROL OF SEX DIFFERENCES IN BRAIN AND BEHAVIOR

这项提议旨在建立神经中枢和细胞机制。 性腺激素通过何种途径促进发声能力和性别差异 雀形目鸟类的神经组织。在斑马雀身上，歌声是一种 通常只由男性产生的雄激素依赖型行为。 雌激素在发育过程中起决定组织的作用， 重要的是，雄激素在宋代区域的积聚程度。 雄激素在成年期诱导进一步的神经生长，并促进歌曲 发展。这项建议侧重于三个重要问题，涉及 歌唱系统的世俗分化。第一个问题是在哪里 雌激素(E2)起到使发展中地区男性化的作用。类固醇 放射自显影将被用来评估哪个发育中的宋区 累积雌二醇组。将使用颅内E2植入物来确定 这些神经部位是雌激素作用的主要靶点，它们是 间接影响，或跨突触影响。第二个问题涉及 雌激素早期暴露如何决定雄激素蓄积的程度和 成人大脑的敏感度。类固醇放射自显影将用于 评估雄激素在发育中的宋代区域内的积累，因此， 雌二醇是否诱导或保持雄激素的阳性模式 积累。E_2这一方面存在一个临界期 行动将通过检查雄激素积累的模式来确定 在成年后给予全身雌激素的鸟类。胸苷放射自显影将会是 用于确定神经发生是否发生在雌二醇的关键期 行动，如果雌二醇刺激这种神经发生。第三个问题涉及 雄激素在老年痴呆中的神经作用部位及其功能意义 成人的大脑。宋代细胞形态的光镜分析 区域和行为分析，雄激素诱导的神经的时间过程 将对变化进行评估，并与声音发展相关。的预测 积累雄激素的细胞将通过同步建立 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SING区域的雄激素积累神经元介导 雄激素诱导其传出靶点的神经生长。更好的 对性别分化的细胞机制的理解 性功能障碍的治疗方法大有希望 人类的分化。这也将增加我们对 允许神经可塑性方面的细胞机制是 在鸟类身上表现出来，但在人类身上就不那么强健了。

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.