Characterization of Sexual Dimorphism in the Brain

大脑性别二态性的表征

• 批准号: 7060320
• 负责人: Nirao Mahesh Shah
• 金额: $ 32.82万
• 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/7060320
• 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）：所有动物都进化出行为，导致对外部世界的天生反应。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，这表明产生它们的神经回路是开发编程的。在性行为的小鼠中，二态行为代表了一组由气味线索和内部调节剂（例如性腺激素）控制的先天行为。 性二态行为是性别之间行为的定性或定量差异，并且要表征介导这些行为反应的神经回路还有许多工作要做。 性别之间的这种先天行为差异是由于性别分化的神经回路而导致的。男性特异性行为需要睾丸激素及其受体，雄激素受体（AR）。我们和其他人观察到质末端床核内神经元库中AR表达的性二态性。该研究建议采用了一种遗传方法来表征这种AR+二态亚群在小鼠性二态行为中的神经元的作用。 该项目将检查AR+ BNST神经元在交配和侵略过程中是否激活了气味线索是否足以激活它们，以及是否利用沃马纳纳纳斯气味检测来中继这些气味提示。使用靶向该项目的基因研究成年动物中消融双态BNST神经元的行为后果。最后，使用遗传策略，该项目将通过删除成年动物中的AR基因来检查AR在双态BNST中的功能。 人类中AR功能的遗传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，抗雄激素疗法或低水平的睾丸激素可能与性欲和情感幸福感丧失有关。我们对BNST神经元中AR缺失的动物的检查原则上应该对神经元如何应对睾丸激素信号的损失有所反应。更笼统地，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觉线索与内部生理状态整合以产生有意义的行为。