Characterizing the role of the medial amygdala in sexually dimorphic behaviors

描述（由申请人提供）：有性繁殖的动物在社会行为方面表现出差异，如交配、亲代照顾和领土侵略。这些二态行为是大脑中分子、细胞和回路水平性别差异的结果。杏仁核是一种非常保守的进化结构，包括在人类中，它被认为控制着情绪和其他本能反应。事实上，杏仁核被认为调节着许多行为，比如恐惧、压力反应、躲避捕食者、交配和攻击。这种功能多样性反映在该区域的细胞和分子异质性上。杏仁核的一个组成部分，内侧杏仁核（MeA），被认为对交配和攻击行为至关重要。我导师的实验室，Shah实验室，已经在MeA中发现了一组离散的神经元，它们是两性二态的，这表明这些神经元可能对交配和战斗的二态表现很重要。与这一观点一致的是，这些神经元（并且只有MeA中的这些神经元）表达芳香酶。芳香酶在男性大脑中将循环中的睾丸激素转化为雌性激素，它的功能对男性典型的交配和侵略表现至关重要。因此，先前的研究表明，双态社会行为需要MeA，而MeA中的神经元子集表达的酶也是这些行为所必需的。我假设这些芳香化酶+ MeA神经元对于交配和攻击的表现是必不可少的。为了验证我的假设，我将以一种有条件的方式从基因上切除雄性和雌性的这些神经元，并测试它们在交配和攻击性方面的变化。这项研究不仅将揭示MeA中芳香化酶+神经元在控制两性二态行为中的功能，而且由于MeA是一个高度进化保守的区域，它很可能与人类健康有关。病理生理学研究证明了杏仁核与许多神经精神疾病的相关性：情绪和焦虑症、自闭症谱系障碍、精神分裂症等等，所有这些疾病都表现出性别差异。我的研究将促进我们对这个重要的、两性二态的大脑区域的基本神经回路和功能的理解，这对人类健康和疾病将是无价的。

DESCRIPTION (provided by applicant): Sexually reproducing animals display differences in social behaviors such as mating, parental care, and territorial aggression. These dimorphic behaviors are a consequence of molecular, cellular and circuit level sex differences in the brain. The amygdala is a deeply conserved evolutionary structure, including in humans, that is thought to control emotions and other instinctual responses. Indeed the amygdala is thought to mediate many behaviors such as fear, stress response, predator avoidance, mating and aggression. This functional diversity is reflected in the cellular and molecular heterogeneity of the region. One component of the amygdala, the medial amygdala (MeA), is thought to be critical for mating and aggressive behavior. My mentor's lab, the Shah Lab, has identified a discrete set of neurons in the MeA that is sexually dimorphic, which suggests that these neurons may be important for dimorphic displays of mating and fighting. Consistent with this idea, these neurons (and only these neurons within the MeA) express the enzyme aromatase. Aromatase converts circulating testosterone into estrogen in the male brain, and its function is essential for male-typical displays of mating and aggression. Thus previous work has shown that the MeA is required for dimorphic social behaviors, and this subset of neurons in the MeA expresses an enzyme that is also required for these behaviors. I hypothesize that these aromatase+ MeA neurons are essential for the display of mating and aggression. To test my hypothesis I will genetically ablate these neurons in a conditional manner in both males and females and test for alterations in mating and aggression. This study will not only shed light on the function of aromatase+ neurons in the MeA in controlling sexually dimorphic behaviors, but because the MeA is a highly evolutionarily conserved region, it is very likely to be pertinent to human health as well. Pathophysiological studies demonstrate the relevance of the amygdala to many neuropsychiatric disorders: mood and anxiety disorders, autism spectrum disorders, schizophrenia, and more, all of which show sex differences. My studies will advance our understanding of basic neural circuitry and function of this important, sexually dimorphic brain region, which will be invaluable to human health and disease. PUBLIC HEALTH RELEVANCE: Pathophysiological studies demonstrate the relevance of the amygdala to many neuropsychiatric disorders: mood and anxiety disorders, autism spectrum disorders, schizophrenia, and more, which all show sex differences. My studies will advance our understanding of basic neural circuitry and function of this important, sexually dimorphic brain region, which will be relevant to human health and disease.