Mutant studies of aggression in Drosophila

描述（由申请人提供）：攻击性几乎是社会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。在这个建议中，遗传学的方法将被用来检查的侵略使用果蝇，果蝇，作为实验模型。随着基因组测序，丰富的强大的遗传学方法可用，并认识到类似的基因以类似的方式在所有动物物种中使用，包括人类，对果蝇的研究应该为理解这种复杂的行为模式提供重要信息。目前研究的长期目标是确定基因和分子，神经元亚型，以及果蝇攻击中重要的神经元通路。 为了实现这些目标，本申请有四个具体目标。I.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;（2）是否有关于社会地位的长期和/或短期记忆，作为赢得或失去打架的结果。二.像血清素这样的胺与大多数动物的攻击性有关。将产生突变的果蝇品系，其中大脑中的胺神经元功能可以通过温度的微小变化而关闭和打开。 强大的GAL 4/UAS系统将用于此目的，我们将选择性地修饰5-羟色胺、多巴胺和章鱼胺神经元的功能，以观察对战斗行为的影响。三.假设像大多数物种一样，会有社会地位的记忆：（1）将在苍蝇中检查战斗行为，其中蘑菇体（在果蝇的记忆中重要的脑区域）已经被化学消融;（2）在学习突变果蝇品系中检查战斗行为;（3）GAL 4细胞系将被用于检查可逆性消融蘑菇体神经元亚群对战斗行为的影响。四.帕金森氏症和阿尔茨海默氏症/额颞叶痴呆症疾病模型已经在苍蝇中产生，通过创建具有已知参与人类这些疾病的蛋白质的转基因动物。与这些疾病相关的一种表型是增强的攻击性。苍蝇模型将被检查，看看他们是否也显示出增强的侵略性。

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.