Neurobiology of Female Aggression

女性攻击性的神经生物学

• 批准号: 1856724
• 负责人: Robert Meisel
• 金额: $ 65万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1856724&HistoricalAwards=false
• 关键词: Neurobiology; Female; Aggression

Public Award AbstractEveryone knows that among mammals males are aggressive and females are not. Despite the common knowledge, this is a misconception that was born from testing and observing animal social behavior is situations that favored males to be aggressive. Female mammals are indeed aggressive, though in different circumstances than are males. This long-standing, but incorrect view, of sex differences in aggression has hindered our understanding of the biology underlying aggression in females. This research is therefore highly innovative in its concept and as well as its goal to correct the imbalance in our knowledge of the neuroscience of female aggression. The research will address a specific set of hypotheses targeted at brain sites regulating aggression in female animals. Within the nerve cells (neurons) in these brain areas, fluctuations in the balance of specific chemical reactions are proposed to regulate whether or not female animals engage in aggression. Finally, the idea that the nerve cells physically change as a result of repeated aggressive encounters (at least for the winners of those encounters) will be tested. Beyond the research itself and communicating the results of the research to the public, the research program will be used to foster science education in the classroom, provide public outreach in the form of community events and lectures, and to generate interest in scientific careers for undergraduate students.The research in this proposal is designed to uncover news insights into the regulation of female aggression in several realms. It is well known that winning an aggressive encounter increases the likelihood that females will be aggressive in future encounters. This experience-based escalation of aggression correlates with increased dendritic spine density in medium spiny neurons of the nucleus accumbens, a novel finding for either males or females. Underlying this structural plasticity are changes in mTOR and FMRP signaling following aggressive experiences. This research identifies a natural role for FMRP and its regulation of neuronal plasticity beyond the pathology of fragile X syndrome, a research direction that is another innovative component of the proposed research. Further, the research in this proposal is designed to identify a functional link between aggression, intracellular signaling and structural changes in the nucleus accumbens. Overall, the research will test the novel hypothesis that there is a feed-forward process with repeated aggressive experience in females that escalates aggression in future encounters, thus increasing dominance and ultimately reproductive success. This behavioral process requires neuronal signaling that produces long-term plasticity in the nucleus accumbens. Collectively, the research will develop a detailed understanding of the neurobiology of female aggression, yielding a transformational shift in how we view aggression in female mammals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

每个人都知道，在哺乳动物中，雄性具有攻击性，而雌性则不然。尽管这是常识，但这是一种误解，来自于测试和观察动物的社会行为，即倾向于雄性具有攻击性的情况。雌性哺乳动物确实具有攻击性，尽管在不同的环境下与雄性不同。这种长期存在但不正确的观点，认为性别在攻击性上的差异阻碍了我们对女性攻击性的生物学基础的理解。因此，这项研究在概念上具有高度创新性，其目标是纠正我们对女性攻击性神经科学知识的不平衡。这项研究将针对调节雌性动物攻击性的大脑部位提出一系列特定的假设。在这些大脑区域的神经细胞（神经元）内，特定化学反应平衡的波动被提出来调节雌性动物是否参与攻击。最后，神经细胞的物理变化是由于反复的攻击性遭遇（至少对那些遭遇的赢家来说）的结果，这一观点将得到验证。除了研究本身和向公众传达研究结果之外，该研究项目还将用于促进课堂上的科学教育，以社区活动和讲座的形式提供公众宣传，并激发本科生对科学事业的兴趣。本提案中的研究旨在揭示在几个领域中对女性攻击性的调节的新见解。众所周知，赢得一场激烈的战斗会增加雌性在未来的战斗中表现出攻击性的可能性。这种基于经验的攻击性升级与伏隔核中棘神经元的树突棘密度增加有关，这是对男性或女性的新发现。这种结构可塑性的基础是攻击经历后mTOR和FMRP信号的变化。本研究确定了FMRP在脆性X综合征病理之外的自然作用及其对神经元可塑性的调节，这是本研究的另一个创新组成部分。此外，本提案的研究旨在确定攻击，细胞内信号传导和伏隔核结构变化之间的功能联系。总的来说，这项研究将测试一个新的假设，即雌性在重复的攻击经历中存在一个前馈过程，该过程会在未来的遭遇中升级攻击，从而增加优势，最终实现繁殖成功。这种行为过程需要在伏隔核中产生长期可塑性的神经元信号。总的来说，这项研究将对雌性攻击性的神经生物学有一个详细的了解，从而使我们对雌性哺乳动物攻击性的看法发生根本性的转变。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。