Characterizing the role of the medial amygdala in sexually dimorphic behaviors

描述内侧杏仁核在性二态性行为中的作用

• 批准号: 8314691
• 负责人: Elizabeth K. Unger
• 金额: $ 3.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314691
• 关键词: Aggressive behavior; Amygdaloid structure; Animals; Anxiety; Anxiety Disorders; Aromatase; Behavior; Biological Assay; Blood Circulation; Brain; Brain region; Caring; Cells; Complex; Cues; Dependovirus; Disease; Emotional; Emotions; Engineering; Enzymes; Estrogens; Female; Fright; Functional disorder; Genetic; Goals; Health; Heterogeneity; Human; Incidence; Light; Link; Medial; Mediating; Memory; Mentors; Molecular; Mood Disorders; Mouse Strains; Mus; Neurons; Neurophysiology - biologic function; Ovary; Partner in relationship; Pattern; Pheromone; Post-Traumatic Stress Disorders; Role; Schizophrenia; Severities; Sex Behavior; Sex Characteristics; Social Behavior; Source; Stress; Structure; Testing; Testosterone; Time; Woman; Work; autism spectrum disorder; biological adaptation to stress; caspase-3; cohort; fighting; insight; male; maternal aggression; mature animal; men; neural circuit; neuron apoptosis; neuropsychiatry; research study; response; social; tool

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.

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，父母照顾和领土侵略。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，包括人类在内，被认为控制情绪和其他本能反应。事实上，杏仁核被认为是介导许多行为，如恐惧，压力反应，捕食者回避，交配和侵略。这种功能多样性反映在该区域的细胞和分子异质性中。杏仁核的一个组成部分，内侧杏仁核（MeA），被认为是交配和攻击行为的关键。我的导师的实验室，沙阿实验室，已经确定了一组离散的神经元在MeA是性二态的，这表明这些神经元可能是重要的交配和战斗的二态显示。与这个想法一致，这些神经元（并且只有MeA内的这些神经元）表达芳香酶。芳香化酶在男性大脑中将循环中的睾丸激素转化为雌激素，它的功能对于男性典型的交配和攻击表现至关重要。因此，先前的工作已经表明，MeA是双态性社会行为所必需的，并且MeA中的这一神经元子集表达了这些行为所必需的酶。我假设这些芳香化酶+ MeA神经元是必不可少的交配和侵略的展示。为了验证我的假设，我将以有条件的方式在男性和女性中基因消融这些神经元，并测试交配和攻击的变化。这项研究不仅揭示了MeA中芳香化酶+神经元在控制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，它也很可能与人类健康有关。病理生理学研究表明，杏仁核与许多神经精神障碍相关：情绪和焦虑障碍、自闭症谱系障碍、精神分裂症等，所有这些都显示出性别差异。我的研究将促进我们对这个重要的、性别二态性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非常宝贵的。 公共卫生相关性：病理生理学研究表明，杏仁核与许多神经精神障碍相关：情绪和焦虑障碍、自闭症谱系障碍、精神分裂症等，这些都显示出性别差异。我的研究将促进我们对这个重要的、性别二态性大脑区域的基本神经回路和功能的理解，这将与人类健康和疾病有关。