Characterization of Sexual Dimorphism in the Brain

大脑性别二态性的表征

• 批准号: 6986519
• 负责人: Nirao Mahesh Shah
• 金额: $ 33.65万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986519
• 关键词: aggression; androgen receptor; animal communication behavior; behavior; behavioral /social science research tag; cues; gender difference; gene expression; gene targeting; hormone regulation /control mechanism; laboratory mouse; olfactions; psychophysiology; reproduction; sensory mechanism; testosterone; vomeronasal systems

DESCRIPTION (provided by applicant): All animals have evolved behaviors that result in innate responses to the external world. These responses can often be observed without prior learning or experience, suggesting that the neural circuits that generate them are developmentally programmed. In mice sexually dimorphic behaviors represent a set of innate behaviors that are controlled by odorant cues and by internal regulators such as gonadal hormones. Sexually dimorphic behaviors are qualitative or quantitative differences in behavior between the sexes, and much work remains to be done to characterize the neural circuits that mediates these behavioral responses. Such innate behavioral differences between the sexes result from sexually differentiated neural circuits. Testosterone and its receptor, the androgen receptor (AR), are required for male-specific behaviors. We and others observe sexual dimorphism in AR expression in a pool of neurons within the bed nucleus of the stria terminalis. This research proposal takes a genetic approach to characterize the role of this AR+ dimorphic subpopulation of neurons in sexually dimorphic behaviors in mice. This project will examine whether the AR+ BNST neurons are activated during mating and aggression, whether odorant cues are sufficient to activate them, and whether vomeronasal odorant detection is utilized to relay these odorant cues. Using gene targeting this project examines the behavioral consequences of ablating the dimorphic BNST neurons in the adult animal. Finally, using a genetic strategy this project will examine the function of AR in the dimorphic BNST by deleting the AR gene in the adult animal. An inherited loss of function of AR in humans manifests as physical and behavioral feminization (androgen insensitivity syndrome). In adult humans anti-androgen therapy or low levels of testosterone may be associated with a loss of libido and emotional well-being. Our examination of animals with a deletion of AR in BNST neurons should shed some light, in principle, on how neurons respond to a loss of testosterone signaling. More generally, our studies should further our understanding of how discrete brain regions integrate external sensory cues with internal physiological states to generate meaningful behavior.

描述（由申请人提供）：所有动物都进化出了对外部世界产生先天反应的行为。这些反应通常可以在没有事先学习或经验的情况下观察到，这表明产生这些反应的神经回路是经过发育编程的。在小鼠中，两性异形行为代表了一组由气味线索和性腺激素等内部调节因子控制的先天行为。 性别二态性行为是两性之间行为的定性或定量差异，仍然需要做很多工作来表征介导这些行为反应的神经回路。 两性之间这种先天的行为差异是由性别差异的神经回路造成的。睾酮及其受体雄激素受体 (AR) 是男性特有行为所必需的。我们和其他人观察到终纹床核内的一组神经元中 AR 表达的性别二态性。该研究计划采用遗传学方法来表征 AR+ 神经元二态性亚群在小鼠性二态性行为中的作用。 该项目将检查 AR+ BNST 神经元在交配和攻击过程中是否被激活，气味线索是否足以激活它们，以及犁鼻气味检测是否用于传递这些气味线索。该项目利用基因靶向研究消除成年动物二态性 BNST 神经元的行为后果。最后，该项目将使用遗传策略，通过删除成年动物中的 AR 基因来检查二态性 BNST 中 AR 的功能。 人类遗传性 AR 功能丧失表现为身体和行为女性化（雄激素不敏感综合征）。在成年人中，抗雄激素治疗或睾酮水平低可能与性欲和情绪健康的丧失有关。我们对 BNST 神经元中 AR 缺失的动物进行的检查，原则上应该可以揭示神经元如何响应睾酮信号传导的缺失。更一般地说，我们的研究应该进一步了解离散的大脑区域如何将外部感官线索与内部生理状态结合起来以产生有意义的行为。