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

项目摘要： 攻击性是一种正常的先天行为，用于获得食物，领土和配偶，基本上所有 动物，包括人类。攻击性的表现程度因人而异， 然而，一般来说，不知道这种异质性有多少是遗传的，多少是社会的， 诱导。也许这两种机制都影响着所有生物体的行为表达， 每个人之间的比例差异很大。以暴力形式进行的肆无忌惮的侵略， 这种行为的特殊人类表现，当一个人使用能够造成 对个人和群体的致命伤害，是一个严重的社会问题。事实上，武器 让最不健康的人成为我们社会的主导者。在动物物种中， 同种有时也会杀死对手，但更常见的是同一物种的成员参与 在仪式上逐步增加战斗能力的强度。侵略的根源是生物学的 但是关于暴力的种子是如何以及在神经系统的什么地方的， 播种在这个应用程序中，我们使用了我们率先使用的果蝇攻击模型。所有 在现有的模型中，果蝇系统为遗传操作提供了最大的方便性和可重复性 在神经系统中，可以精确到单个神经元的水平。这些操作可以很容易地 结合可量化的行为测量来试图理解这种复杂的行为。最近， 使用交叉遗传学策略，我们在活体中鉴定并操纵单胺神经元， 有攻击性的动物例如，一对多巴胺能（5 HT）神经元通过 这种技术，促进了在战斗中更高层次的侵略性。第一个周期 应用程序，我们解开了一些复杂的电路与这种促进。这个神经元支配 苍蝇大脑中感觉整合中心的一个小视觉区域。该区域的输出是“开关”， 增强或减少更高水平的攻击性，而通过释放5 HT激活该“开关”是 增强子元件最近的其他研究表明，雌性果蝇也可以在高强度水平上战斗， （以前我们认为雌性只在低强度下战斗），两对胆碱能神经元被 只有女性大脑中才有这种决定。最近的其他研究表明，苍蝇， 预期，使用感官线索来决定如何表现（例如，战斗或法庭），但也观察和观察 其他动物在做决定时的行为。在本建议中，我们继续这些 研究通过询问：如何在雄性和雌性苍蝇中引发高水平的攻击;电路如何 不同的性别;以及如何观察到的性别选择行为模式的差异产生。 该应用程序还试图解决我们从科学和模式生物研究中学到的东西是否可以 有助于解释围绕人类暴力根源的严重紧迫问题的一小部分？

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?