Characterization of Sexual Dimorphism in the Brain

描述（由申请人提供）：所有动物都有进化的行为，导致对外部世界的先天反应。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发育编程的。在小鼠中，性二态行为代表了一组由气味线索和内部调节因子（如性腺激素）控制的先天行为。 性二态行为是两性之间行为的质或量的差异，还有很多工作要做，以表征介导这些行为反应的神经回路。 两性之间的这种先天行为差异是由性分化的神经回路造成的。睾酮及其受体，雄激素受体（AR），是男性特有的行为所必需的。我们和其他人在终纹床核内的神经元池中观察到AR表达的两性异形。这项研究计划采用遗传学方法来表征这种AR+双态神经元亚群在小鼠性双态行为中的作用。 该项目将研究AR+ BNST神经元是否在交配和攻击过程中被激活，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技术研究了消融成年动物二态BNST神经元的行为后果。最后，利用遗传策略，本项目将通过删除成年动物中的AR基因来检查AR在二型BNST中的功能。 人类AR功能的遗传性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，抗雄激素治疗或低水平的睾酮可能与性欲和情感健康的丧失有关。我们对BNST神经元中AR缺失的动物进行的研究，原则上应该有助于了解神经元如何对睾酮信号丢失做出反应。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整合外部感官线索与内部生理状态，以产生有意义的行为。

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.