Mutant studies of aggression in Drosophila

描述(申请人提供)：攻击性几乎是群居动物行为的普遍特征。在野外，它被用来获取食物和住所，保护自己免受捕食和选择配偶。尽管它很重要，但人们对这种行为背后的神经机制知之甚少。在这项建议中，将使用果蝇作为实验模型，采用遗传学方法来检查攻击性。随着基因组测序，大量强大的遗传方法可用，并认识到类似的基因在包括人类在内的所有动物物种中以相似的方式使用，对果蝇的研究应该会产生重要的信息，以理解这种复杂的行为模式。目前研究的长期目标是确定果蝇攻击行为中重要的基因和分子、神经元亚型和神经元通路。为了实现这些目标，该应用程序有四个具体目标。行为研究将解决以下问题：(1)女性是否会打架，她们的行为是否可以被分析；以及(2)是否会因为打架的胜负而对社会地位产生长期和/或短期的记忆。像5-羟色胺这样的胺被认为与大多数动物的攻击性有关。将产生突变的苍蝇系，在这些系中，大脑中的胺神经元功能可以通过温度的微小变化来关闭和打开。为此，我们将使用功能强大的GAL4/UAS系统，并选择性地对5-羟色胺、多巴胺和章鱼胺神经元的功能进行修饰，以观察其对战斗行为的影响。假设像大多数物种一样，会有社会地位的记忆：(1)对蘑菇体(果蝇记忆中重要的大脑区域)进行化学消融的果蝇的战斗行为进行研究；(2)在学习突变果蝇品系的过程中研究战斗行为；(3)将使用GAL4品系来研究可逆性消融蘑菇体神经元亚群对战斗行为的影响。通过创造含有已知与人类这些疾病有关的蛋白质的转基因动物，在果蝇中产生了帕金森氏症和阿尔茨海默氏症/额颞叶痴呆症疾病模型。与这些疾病相关的一个表型是攻击性增强。将对苍蝇模型进行检查，看看它们是否也表现出更强的攻击性。

DESCRIPTION (provided by applicant): Aggression is a nearly universal feature of the behavior of social animals. In the wild, it is used for access to food and shelter, for protection from predation and for selection of mates. Despite its importance, little is known of the neural mechanisms that underlie the behavior. In this proposal a genetic approach will be taken to the examination of aggression using the fruit fly, Drosophila melanogaster, as the experimental model. With the genome sequenced, with a wealth of powerful genetic methods available, and with the recognition that similar genes are used in similar ways in all species of animals, including humans, studies with fruit flies should yield important information towards understanding this complex pattern of behavior. The long-term goals of the present studies are to identify genes and molecules, subtypes of neurons, and neuronal pathways important in aggression in fruit flies. Towards these goals, this application has four Specific Aims. I. Behavioral studies will address the questions: (1) Do females fight and can their behavior be analyzed; and (2) Are there long- and/or short-term memories of social status as a consequence of winning or losing fights. II. Amines like serotonin have been implicated in aggression in most species of animals. Mutant fly lines will be generated in which amine neuron function can be turned off and on in the brain by small changes in temperature. The powerful GAL4/UAS system will be used for this purpose, and we will selectively modify the function of serotonin, dopamine and octopamine neurons to observe the effects on fighting behavior. III. Assuming that as in most species, there will be a memory of social status: (1) fighting behavior will be examined in flies in which mushroom bodies (brain areas important in memory in flies) have been chemically ablated; (2) fighting behavior will be examined in learning mutant fly lines; and (3) GAL4 lines will be used to examine the effects on fighting behavior of reversibly ablating subsets of mushroom body neurons. IV. Parkinson's and Alzheimer's/Frontotemporal Dementia disease models have been generated in flies by creating transgenic animals with proteins known to be involved in these diseases in humans. One phenotype associated with these disorders is enhanced aggression. The fly models will be examined to see if they too show enhanced aggression.