Characterization of Sexual Dimorphism in the Brain

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，这表明产生它们的神经回路是发育编程的。在小鼠中，两性二态行为代表了一系列先天行为，这些行为受气味线索和性腺激素等内部调节因素的控制。两性二态行为是两性之间在行为上的定性或定量差异，对调节这些行为反应的神经回路进行表征仍有许多工作要做。这种天生的性别行为差异是由不同性别的神经回路造成的。睾丸激素及其受体雄激素受体（AR）是男性特有行为所必需的。我们和其他人在终纹床核内的一个神经元池中观察到AR表达的性别二态性。本研究计划采用遗传方法来表征这种AR+二态神经元亚群在小鼠性二态行为中的作用。

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.