HORMONAL CONTROL OF SEX DIFFERENCES IN BRAIN

这项提议旨在建立神经站点和 类固醇促进性别差异的细胞机制 在发声能力和神经组织方面。在斑马雀身上， 歌唱行为依赖于雄激素，正常情况下只产生 被男性杀死。雌激素在发育过程中起作用，以确定 雄激素在歌唱中积累的组织和程度 地区。雄激素在成年后会进一步促进神经生长， 促进歌曲发展。这项建议主要集中在三个方面 关于性别分化的重要问题 歌唱系统。第一个问题是雌激素(E2)在哪里起作用 使发展中的歌唱地区男性化。类固醇放射自显影 将被用来评估哪些发展中的歌曲区域积累 E2。将使用颅内E2植入物来确定 这些神经部位是E2作用的主要靶点，并且 它们受到间接或跨突触的影响。这个 第二个问题是关于早期的E2暴露如何决定 成人大脑中雄激素摄取的程度。最新研究 表明在一个歌唱区域，早期的E2暴露促进了 青春期雄激素靶细胞的增加。 将使用胸腺嘧啶核苷放射自显影技术来确定 细胞添加涉及神经发生，以及雌二醇是否会增强 这一区域内细胞的增殖或存活。 雌激素临界期的存在 雄激素积累的调节将由以下因素决定 研究注射雌二醇的鸟类对雄激素的摄取模式 成人期。第三个问题涉及神经部位和 雄激素在成人大脑中作用的功能意义。 SONE细胞形态的光镜分析 区域，和行为分析，时间进程 雄激素诱导的神经变化将被评估并与 声音的发展。雄激素蓄积细胞的投射 将通过同时使用荧光来建立 逆行示踪剂和类固醇放射自显影 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。一个 更好地理解性别分化过程 为人类畸形的治疗带来巨大的希望 人类的性别分化。它还将增加我们的 对细胞机制的理解允许在某些方面 在鸟类身上表现出的神经可塑性，但不那么健壮 在人类身上。

This proposal is aimed at establishing neural sites and cellular mechanisms by which steroids promote sex differences in vocal ability and neural organization. In zebra finches, song behavior is androgen-dependent and normally produced only by males. Estrogens act during development to determine the organization and extent of 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 sexual differentiation of the song system. The first regards where estrogen (E2) acts to masculinize developing song regions. Steroid autoradiography will be used to assess which developing song regions 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 transynaptically. The second issue concerns how early E2 exposure determines the extent of androgen uptake in the adult brain. Recent studies indicate that in one song region, early E2 exposure promotes the addition of androgen target cells during adolescence. Thymidine autoradiography will be used to determine if this cell addition involves neurogenesis, and whether E2 enhances either the proliferation or survival of cells in this region. The existence of a critical period for the estrogenic regulation of androgen accumulation will be determined by examining the pattern of androgen uptake in birds given E2 in adulthood. 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 sone regions, and behavioral analyses, the time course of androgen-induced nerual change will be assessed and related to vocal development. Projections of androgen-accumulating cells will be established through 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 sexual differentiation process holds 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.