Mutant studies of aggression in Drosophila

果蝇攻击性的突变研究

• 批准号: 7115123
• 负责人: Edward A Kravitz
• 金额: $ 8.23万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115123
• 关键词: Drosophilidae; aggression; amines; arthropod genetics; behavior test; behavioral genetics; dopamine; ethology; gender difference; gene mutation; genetically modified animals; memory; octopamine; serotonin

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.

描述（由申请人提供）：攻击性几乎是社会性动物行为的普遍特征。在野外，它被用来获取食物和住所、防止被捕食和选择配偶。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。在该提案中，将采用遗传方法来使用果蝇（Drosophila melanogaster）作为实验模型来检查攻击性。通过基因组测序，利用丰富的强大的遗传方法，并认识到相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，对果蝇的研究应该为理解这种复杂的行为模式提供重要的信息。 。本研究的长期目标是确定在果蝇攻击行为中重要的基因和分子、神经元亚型以及神经元通路。 为了实现这些目标，该应用程序有四个具体目标。一、行为研究将解决以下问题：（1）女性会打架吗？可以分析她们的行为吗？ (2) 是否因打架的输赢而产生对社会地位的长期和/或短期记忆。二.血清素等胺类物质与大多数动物的攻击行为有关。将产生突变蝇系，其中可以通过温度的微小变化来关闭和打开大脑中的胺神经元功能。 强大的GAL4/UAS系统将用于此目的，我们将选择性地修改血清素、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．假设与大多数物种一样，将存在社会地位记忆：（1）将检查蘑菇体（果蝇记忆中重要的大脑区域）已被化学消融的果蝇的战斗行为； (2)学习突变蝇系时将考察战斗行为； (3) GAL4 系将用于检查可逆消融蘑菇体神经元子集对战斗行为的影响。四．帕金森氏症和阿尔茨海默氏症/额颞叶痴呆疾病模型是通过使用已知与人类这些疾病有关的蛋白质创建转基因动物而在果蝇中产生的。与这些疾病相关的一种表型是攻击性增强。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。