Neural Analysis of Maternal Aggression

描述（由申请人提供）：为了帮助理解和减轻人类的攻击，开发适当的动物模型来理解所有不同形式的攻击是至关重要的。母性攻击是哺乳期雌性啮齿动物在保护幼崽时对入侵者表现出的激烈攻击，这可能与人类其他短暂但激烈的攻击形式有相似之处。这项研究由一位新研究者提出，目的是研究小鼠母性攻击的神经基础。在哺乳期，促肾上腺皮质激素释放激素（CRH）神经传递的减少与恐惧和焦虑的减少有关。因为当恐惧和焦虑较低时，母性的攻击性较高，所以恐惧的减少可能是大坝能够攻击通常引起恐惧的刺激所必需的。尽管这可能与母亲的攻击性有关，但没有工作系统地研究CRH是否或如何在控制这一重要的社会行为中发挥作用。本研究验证了哺乳期间CRH的调节在母体攻击性的开启中发挥必要作用的假设。与这一假设一致，我们收集的证据表明，脑室内注射CRH抑制母体攻击，并且由于发育干预导致内源性CRH的减少增加了母体攻击水平。这三项研究将扩展这些初步发现，并使用多种方法进一步研究CRH在母亲攻击中的作用。1)侧脑室静脉注射CRH及相关肽尿皮质素III和两种CRH受体拮抗剂，确定对母体攻击的影响。2)检查由于发育干预而表现出母性攻击水平增加的小鼠中CRH mRNA水平是否以及在何处下降。3)检测缺失CRH受体1基因或CRH受体2基因的小鼠相对于对照组小鼠的母性攻击水平。每项研究还将使用神经元活动的间接标记物，cFOS和FosB，来确定CRH可能与母体攻击回路相互作用的大脑区域。许多研究都集中在雄性攻击上，但对雌性攻击的神经基础知之甚少，初步结果表明CRH对雄性和雌性攻击具有相反的作用。因此，对攻击性方面的性别差异进行基础研究，对于理解社会行为、健康和疾病方面的性别差异和性别差异的生物学基础非常重要。

DESCRIPTION (provided by applicant): To help understand and mitigate human aggression, it is critical to develop appropriate animal models to understand all the different forms of aggression. Maternal aggression is a fierce aggression exhibited towards intruders by lactating female rodents when they are protecting their pups, that may share similarities with other short-lived, but fierce forms of human aggression. The goal of this proposed research, submitted by a new investigator, is to examine the neural basis of maternal aggression in mice. During lactation, decreases in corticotropin releasing hormone (CRH) neurotransmission have been linked to decreases in fear and anxiety. Because maternal aggression is high when fear and anxiety are low, it is possible that decreases in fear are necessary for a dam to be able to attack a normally fear evoking stimulus. Despite a possible link to maternal aggression, no work has systematically examined whether, or how, CRH plays a role in the control of this important social behavior. The studies proposed here test the hypothesis that regulation of CRH during lactation plays a necessary role in switching on maternal aggression. Consistent with this hypothesis we have collected evidence that intracerebroventricular (icv) injections of CRH inhibit maternal aggression and that decreases in endogenous CRH due to developmental intervention increase levels of maternal aggression. The three studies of this proposal will extend these preliminary findings and use multiple approaches to investigate further the role of CRH in maternal aggression. 1) Conduct icv injections of CRH, and a related peptide, urocortin III, and two CRH receptor antagonists to the lateral ventricle to determine the effect on maternal aggression. 2) Examine whether and where levels of CRH mRNA are decreased in mice that exhibit increased levels of maternal aggression due to a developmental intervention. 3) Examine levels of maternal aggression in mice that are missing either the CRH receptor 1 gene, or the CRH receptor 2 gene relative to control mice. Each study will also use indirect markers for neuronal activity, cFOS and FosB, to identify brain regions where CRH may be interacting with maternal aggression circuitry. Many studies have focused on male aggression, but far less is known about the neural basis of female aggression and preliminary results indicate that CRH has the opposite effect on male and maternal aggression. Basic research into sex differences in aggression, then, is important to understanding the biological underpinnings of sex and gender differences in social behavior, health, and disease.