Mutant Studies of Aggression in Drosophila

果蝇攻击性的突变研究

• 批准号: 7921249
• 负责人: Edward A Kravitz
• 金额: $ 21.28万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921249
• 关键词: 3-Dimensional; Address; Aggressive behavior; Amines; Animal Model; Animals; Arts; Behavior; Behavioral; Behavioral Genetics; Biological; Biological Models; Brain; Cells; Complex; Conflict (Psychology); Courtship; Decision Making; Drosophila genus; Drosophila melanogaster; Female; Ganglia; Genes; Genetic; Genome; Hormones; Human; Individual; Instinct; Laboratories; Maps; Methods; Modeling; Myxoid cyst; Nervous system structure; Neurons; Octopamine; Organism; Output; Pathway interactions; Pattern; Peptides; Plant Roots; Process; Relative (related person); Research Personnel; Research Support; Resolution; Social Environment; Specific qualifier value; Synapses; System; Taiwan; Taste Perception; Transgenic Organisms; Work; court; experience; experimental analysis; fighting; fly; genetic analysis; genetic manipulation; male; mature animal; mutant; neural circuit; octopamine receptor; presynaptic; public health relevance; receptor; response; sex; social

DESCRIPTION (provided by applicant): Aggression is a complex behavior expressed in many different social contexts. Often abused, yet essential for the survival of organisms, little is known of the biological roots of this behavior. While model systems may not duplicate aggression in all of its many human manifestations, they can be highly informative about: the relative importance of genes, hormones and experience in laying down patterns of aggression in nervous systems; detailing the neural circuitry involved; and addressing questions of how animals choose among the varied complex behaviors available within their behavioral repertoires. It is the last two matters that are the major focus of the present application. In recent years, the Kravitz laboratory has established a fruit fly model of aggression making this important behavior available for experimental analysis in an organism that is highly suitable for genetic analysis. With fruit flies aggression is complex and is shown by both males and females, the animals engage in many other inter-related behaviors, and the behaviors can be quantitatively analyzed. In addition, however, the genome has been sequenced and incredibly powerful methods are available that allow experimental manipulations to be performed with fruit flies that cannot yet even be approximated in most other animal model systems. Recently, it has been found that the same gene that determines who flies court also determines whether flies fight like males or females. The present application extends these studies and has the following Specific Aims: I. To explore decision-making between courtship and aggression, two sexually dimorphic patterns of behavior in flies, by mapping and manipulating the fruitless/doublesex-associated circuitry within the subesophageal ganglion (SOG), the taste center in fruit fly brains; II. To map the distribution of receptors for amines and peptides associated with the SOG circuitry; and III. To introduce genes into neurons that can alter the function of these nerve cells in behaving animals and to begin to address the question of how the same neurons differ in male and female animals. These studies use a wide variety of state-of-the-art genetic, behavioral and anatomical methods in exploring these Aims. For example, in collaborative studies with the Chiang laboratory in Taiwan, neuronal maps will be made that will allow examination in great detail of the possible connections between individual neurons involved in courtship and aggression. The focus will be to define the brain circuitry important in aggression and courtship at much higher levels of resolution than are now available, and then to ask how that circuitry gets established in fly brains and how animals choose between behavioral responses when conflict situations arise. PUBLIC HEALTH RELEVANCE: All organisms, including humans, must be capable of rapidly evaluating social situations and selecting proper responses from what may be a wide variety of possible behavioral choices. Such selections must be made correctly in order to allow the survival of organisms both as individuals and as species. How organisms make such choices and how patterns of innate behavior of great complexity get established in nervous systems are not well understood, and are the theme of this application.

描述（由申请人提供）：攻击性是一种复杂的行为，在许多不同的社会背景下都有表现。经常被滥用，但对于生物体的生存至关重要，但人们对这种行为的生物学根源知之甚少。虽然模型系统可能无法复制人类所有的攻击性表现，但它们可以提供大量信息：基因、激素和经验在神经系统中制定攻击性模式的相对重要性；详细说明所涉及的神经回路；并解决动物如何在其行为库中的各种复杂行为中进行选择的问题。最后两个问题是本申请的主要焦点。近年来，克拉维茨实验室建立了果蝇攻击性模型，使这一重要行为可用于在非常适合遗传分析的生物体中进行实验分析。果蝇的攻击行为很复杂，雄性和雌性都会表现出来，动物会进行许多其他相互关联的行为，并且这些行为可以定量分析。然而，此外，基因组已经被测序，并且可以使用令人难以置信的强大方法，允许对果蝇进行实验操作，而这在大多数其他动物模型系统中甚至还无法近似。最近，人们发现，决定苍蝇求爱的基因也决定了苍蝇是否喜欢雄性或雌性打架。本申请扩展了这些研究，并具有以下具体目标： I.通过绘制和操纵食管下神经节（SOG）（果蝇大脑中的味觉中心）内的无果/双性相关回路，探索求爱和攻击（果蝇的两种性别二态性行为模式）之间的决策；二.绘制与 SOG 电路相关的胺和肽受体的分布图；和三。将基因引入神经元，这些基因可以改变行为动物中这些神经细胞的功能，并开始解决雄性和雌性动物中相同神经元有何不同的问题。这些研究使用各种最先进的遗传、行为和解剖学方法来探索这些目标。例如，在与台湾蒋实验室的合作研究中，将制作神经元图谱，以便详细检查涉及求爱和攻击的各个神经元之间可能的联系。重点是以比现在高得多的分辨率来定义在攻击和求偶中重要的大脑回路，然后询问该回路如何在果蝇大脑中建立，以及动物在发生冲突情况时如何在行为反应之间进行选择。公共卫生相关性：包括人类在内的所有生物体都必须能够快速评估社会状况，并从各种可能的行为选择中选择适当的反应。必须正确地做出这样的选择，以便有机体作为个体和物种能够生存。生物体如何做出这样的选择以及神经系统中如何建立极其复杂的先天行为模式尚不清楚，但这也是本应用的主题。