Behavioral Regulation of Neuroendocrine Cells

描述：这是一项关于继续担任研究科学家的提案 发展奖，现称为独立科学家奖（K02）。期间 该奖项的前 4 年申请人的研究计划有所扩展 显着。申请人发起了一个新的研究领域，涉及新的 合作和新技术技能。该程序利用了 实验室小鼠作为研究行为神经内分泌学的模型系统。的 鼠标的优势在于其丰富的行为能力 加上对其遗传学的深入了解以及设计能力 并生产基因工程动物。 K02奖项允许申请人 接受神经和分子生物学方面的重要新培训 技术。申请人对性行为的兴趣以及性行为的作用 雄激素芳香化为雌激素，导致这些行为的激活 她开始使用雌激素受体α基因敲除小鼠（ERaKOs）进行研究。 她迄今为止的工作表明，尽管性行为和社会 ERaKO 男性和女性的偏好缺乏，用 多巴胺激动剂阿扑吗啡可以恢复正常行为。这一发现 挑战芳香化雌激素使大脑发育男性化的教条 在产前期间。进一步评估类固醇受体的作用 在性行为的激活中，PI 获得了数次额外的 KO 老鼠；包括雌激素受体β敲除小鼠和Tfm小鼠（雄激素 受体敲除）。在即将到来的 K02 资助期内，PI 将审查 使用各种方法研究性行为的分子基础。这些 包括； 1) 体内微透析检查神经儿茶酚胺反应 一氧化氮和性接触； 2）利用高密度DNA阵列 监测基因表达对激素和/或行为相互作用的反应； 3) 分子小鼠遗传学培训。 K02奖非常 很有价值，因为它使 PI 摆脱了大部分的行政和教学工作 责任。这使她能够花大量时间 同事的实验室学习新技术，并将精力集中在 运行她自己的程序。

DESCRIPTION: This is a proposal for the continuation of a Research Scientist Development Award, now called an Independent Scientist Award (K02). During the first 4 years of this award the applicant's research program has expanded significantly. The applicant initiated a new line of research involving new collaborations and new technical skills. This program takes advantage of the laboratory mouse as a model system to study behavioral neuroendocrinology. The advantages that the mouse offers are the richness of its behavioral repertoire coupled with a superior knowledge of its genetics, and the ability to design and produce genetically engineered animals. The K02 award allowed the applicant to receive significant new training in neuro- and molecular biological techniques. The applicant's interest in sexual behaviors and the role of aromatization of androgen to estrogen in the activation of these behaviors lead her to begin working with the estrogen receptor alpha knockout mouse (ERaKOs). Her work to date has revealed that although sexual behavior and social preferences are deficient in ERaKO males and females, treatment with the dopamine agonist apomorphine can reinstate normal behavior. This finding challenges the dogma that aromatized estrogens masculinize brain development during the prenatal period. To further evaluate the role of steroid receptors in activation of sexual behavior the PI has obtained several additional KO mice; including the estrogen receptor beta knockout and Tfm mice (androgen receptor knockouts). During the upcoming K02 grant period the PI will examine the molecular bases for sexual behavior using a variety of approaches. These include; 1) in vivo microdialysis to examine neural catecholamine responses to nitric oxide and sexual encounters; 2) the use of high-density DNA arrays to monitor gene expression in response to hormones and/or behavioral interactions; and 3) training in molecular mouse genetics. The K02 award is extremely valuable since it frees the PI from much of her administrative and teaching responsibilities. This allows her to spend significant amounts of time in colleagues' laboratories learning new techniques and focus her energy on running her own program.