Aggression in Drosophila: circuitry involved; learning and memory accompanying aggression; and establishing the circuitry of high-level aggression in the brain

果蝇的攻击性：涉及电路；

基本信息

批准号：
10488182
负责人：
Edward A Kravitz
金额：
$ 49.16万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2023-12-31
项目状态：
已结题

项目摘要

Project Summary: Aggression is a normal innate behavior utilized for access to food, territory and mates by essentially all species of animals, including humans. Levels of display of aggression vary widely among individuals, however, and generally it is not known how much of this heterogeneity is genetic and how much is socially induced. Probably both mechanisms influence the expression of the behavior in all organisms, with the proportions of each varying widely between individuals. Unbridled aggression, in the form of violence, is a peculiarly human manifestation of this behavior, and when one adds the use of weapons capable of inflicting deadly damage to individuals and masses of individuals, it is a serious problem in society. Indeed weapons allow the least fit of individuals to become dominant protagonists in our society. In animal species, conspecifics sometimes kill opponents as well, but more commonly members of the same species engage in ritualistic stepwise-increasing-intensity-displays of fighting abilities. The roots of aggression are biological but there is little concrete information of how and where in the nervous system the seeds of violence are sown. In this application we use a Drosophila model of aggression that we pioneered the use of. Of all the available models, the Drosophila system offers the greatest ease and reproducibility of genetic manipulation within the nervous system down to single identified neuron levels. These manipulations can readily be combined with quantifiable behavioral measures in attempts to understand this complex behavior. Recently, using an intersectional genetics strategy, we identified and manipulated single amine neurons in living animals that are involved in aggression. For example, a single pair of serotonergic (5HT) neurons found via this technique, facilitated going to higher levels of aggression during fights. With the first cycle of this application, we unraveled some of the complex circuitry involved with this facilitation. This neuron innervates a small visual area of a sensory integration center in the fly brain. The output of that region is a “switch” the either enhances or reduces higher level aggression, and activation of that “switch” by 5HT release is the enhancer element. Other recent studies showed that female flies also can fight at high intensity levels (previously we thought that females fought only at low intensities) and two pairs of cholinergic neurons were found only in female brains that are the keys to that decision. Other recent studies showed the flies, as expected, use sensory cues in deciding how to behave (e.g., fight or court), but also watch and observe what other animals are doing behaviorally in their decision making. In this proposal we continue these studies by asking: how is high-level aggression triggered in male and female flies; how does the circuitry differ in the two sexes; and how are the observed differences in sex-selective behavioral patterns generated. The application also tries to address whether what we learn from science and study of model organisms can help explain even a small part of the serious pressing issues surrounding the root causes of human violence?

项目概要：攻击性是一种正常的与生俱来的行为，几乎所有动物都会利用攻击性来获取食物、领地和配偶。不同种类的动物，包括人类，表现出攻击性的程度差异很大，然而，一般来说，我们并不知道这种异质性有多少是遗传因素造成的，有多少是社会因素造成的。可能这两种机制都会影响所有生物体的行为表达，其中个体之间每种行为的比例差异很大。这种行为是人类特有的表现，当人们使用能够造成伤害的武器时，对个人和群体造成致命伤害，这确实是社会的一个严重问题。让最不适应的个体成为我们社会中的主角。同种动物有时也会杀死对手，但更常见的是同一物种的成员参与战斗攻击性的根源是生物学上的。但关于暴力种子在神经系统中如何以及在何处产生的具体信息却很少在这个应用程序中，我们使用了我们率先使用的果蝇攻击模型。果蝇系统提供了可用的模型，为基因操作提供了最大的便利性和可重复性这些操作可以很容易地在神经系统内进行到单个已识别的神经元水平。最近，结合可量化的行为测量来理解这种复杂的行为。使用交叉遗传学策略，我们识别并操纵了活体中的单个胺神经元例如，通过发现一对血清素能（5HT）神经元。这种技术有助于在战斗中达到更高水平的攻击性。在应用中，我们揭示了与这种促进有关的一些复杂电路。果蝇大脑中感觉统合中心的一小块视觉区域，该区域的输出是“开关”。增强或减少更高水平的攻击性，通过释放 5HT 来激活该“开关”是其他最近的研究表明，雌性果蝇也可以进行高强度的战斗。（之前我们认为雌性只在低强度下战斗）并且两对胆碱能神经元最近的其他研究表明，仅在女性大脑中发现了这一决定的关键。预期的，使用感官线索来决定如何行事（例如，打架或求爱），但也要观察和观察其他动物在决策过程中的行为方式是什么？在本提案中，我们继续这些内容。通过询问以下问题进行研究：雄性和雌性果蝇的高级攻击性是如何触发的；两种性别的差异；以及观察到的性别选择行为模式的差异是如何产生的。该应用程序还试图解决我们从模式生物的科学和研究中学到的知识是否可以能否帮助解释围绕人类暴力根源的严重紧迫问题的一小部分？