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性，开发适当的动物模型以理解所有不同形式的攻击性至关重要。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，这可能与其他短暂但激烈的人类攻击形式有相似之处。这项由一位新研究者提交的拟议研究的目标是检查小鼠母体攻击的神经基础。在哺乳期间，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，母亲的攻击性较高，所以恐惧的减少可能是母亲能够攻击正常的恐惧诱发刺激所必需的。尽管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。本文提出的研究验证了这一假设，即哺乳期CRH的调节在母亲攻击性的转换中起着必要的作用。与这一假设相一致，我们已经收集到的证据表明，脑室内（icv）注射CRH抑制母亲的侵略和内源性CRH的减少，由于发育干预增加母亲的侵略水平。这三项研究将扩展这些初步研究结果，并使用多种方法进一步研究CRH在母亲攻击中的作用。1)侧脑室注射CRH、相关肽尿皮质素III和两种CRH受体拮抗剂，以确定对母体攻击性的影响。2)检查是否以及在哪里CRH mRNA的水平下降，表现出增加的水平，由于发展干预的母亲侵略的小鼠。3)检查缺失CRH受体1基因或CRH受体2基因的小鼠相对于对照小鼠的母体攻击水平。每项研究还将使用神经元活动的间接标记物cFOS和FosB，以确定CRH可能与母体攻击回路相互作用的大脑区域。许多研究都集中在男性的攻击性，但很少有人知道女性的攻击性的神经基础和初步的结果表明，CRH对男性和母亲的攻击性有相反的影响。因此，对攻击性的性别差异进行基础研究，对于理解性别的生物学基础以及社会行为、健康和疾病方面的性别差异非常重要。

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.