Hormonal Modulation of Aggression in Drosophila

果蝇攻击性的激素调节

• 批准号: 8040316
• 负责人: Edward A Kravitz
• 金额: $ 33.8万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8040316
• 关键词: 3-Dimensional; Afferent Neurons; Aggressive behavior; Amines; Animals; Antibodies; Behavior; Behavioral; Biological Models; Cell Line; Cell Nucleus; Cells; Courtship; Databases; Decision Making; Drosophila genus; Drosophila melanogaster; Effectiveness; Enhancers; Equilibrium; Feeding behaviors; Female; Food; Gene Expression; Generations; Genes; Genetic; Genome; Genomics; Hormonal; Human; Image; Individual; Instinct; Label; Learning; Libraries; Maps; Mate Selections; Membrane; Memory; Methods; Modeling; Names; Nervous system structure; Neuraxis; Neurons; Norepinephrine; Octopamine; Organism; Other Genetics; Output; Phenols; Phenotype; Population; Predatory Behavior; Process; Proteins; RNA Interference; Resources; Role; Serotonin; Sex Behavior; Shelter facility; Site; Social Behavior; Specific qualifier value; Staining method; Stains; Synapses; System; Time; Tryptophan; Tyrosine; analog; combinatorial; court; dopaminergic neuron; feeding; fighting; fly; genetic manipulation; male; neural circuit; neuromechanism; octopamine receptor; protein expression; receptor; recombinase; reconstruction; response; sex; social; tool

DESCRIPTION (provided by applicant): Aggression is an innate behavior that is a nearly universal feature of the social behavior of 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. Over the past decade, we have developed a Drosophila melanogaster model of aggression. In same sex pairing of male and female flies, these animals will compete over resources. Males develop hierarchical relationships while females do not, and learning and memory take place during the male fights. A single gene, fruitless, specifies both how flies fight and who they court. Amines have been shown to be important in aggression in all species of animals examined thus far. Fruit flies are no exception. These studies focus on two major amines found in the fruit fly nervous system: octopamine (OA), the phenol analogue of norepinephrine, is the major amine synthesized from tyrosine; and serotonin (5HT), is the major amine derived from tryptophan. There are approximately 100 OA and 5HT neurons in the Drosophila central nervous system. Of the total OA pool, we have identified a small group of 3 or 4 neurons, that co-express the amine and the male protein forms of Fruitless (FruM/OA neurons). These appear to be involved in the decision made by male flies between courtship and aggression. Here we propose to use state of the art genetic methods and a combinatorial method to unravel the circuitry concerned with the FruM/OA neurons, from sensory input through to behavioral output. 5HT serve roles in aggression (not in initiating fights, but in bringing fights to higher intensity levels), courtship behavior, balance and feeding behavior in flies. We ask here whether we can identify the specific 5HT neurons involved in these behaviors, and then can map the circuitry involving the neuron or neurons concerned with aggression. The project has the following Specific Aims: Aim 1: To generate a data base of the morphological features and functional roles served by individual 5HT, OA and dopamine (DA) neurons. Aim 2: Selective manipulation of FruM/OA neurons and behavioral choice: can we map the circuitry concerned with these neurons. Aim 3: Selective manipulation of individual serotonergic neurons. Can we identify which of the ca. 100 5HT neurons are concerned with each of the behaviors known to be influenced by 5HT? If so, can we then map the circuitry involved with 5HT and aggression, the same way we plan to map the FruM/OA circuitry. Studies exploring the roles of amine neurons in behavior at this level of detail just are not possible with other model systems at the present time. PUBLIC HEALTH RELEVANCE: All organisms, including humans, must be capable of rapidly evaluating social situations and of selecting proper responses from a wide variety of possible behavioral choices. Such selections must be correctly made to allow the survival of organisms as individuals or as a species. How organisms make such choices and how the underlying neural circuitry involved in decision making is constructed are the themes of this application.

描述（由申请人提供）：攻击性是一种天生的行为，几乎是动物社会行为的普遍特征。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。尽管它的重要性，但人们对这种行为背后的神经机制知之甚少。在过去的十年里，我们已经开发了一个果蝇攻击模型。在雌雄果蝇的同性配对中，这些动物会争夺资源。男性发展等级关系，而女性没有，学习和记忆发生在男性的战斗。一个单一的基因，没有结果，既指定苍蝇如何战斗，他们的法院。胺已被证明是重要的侵略在所有物种的动物检查到目前为止。果蝇也不例外。这些研究集中在果蝇神经系统中发现的两种主要胺：章鱼胺（OA），去甲肾上腺素的酚类似物，是由酪氨酸合成的主要胺; 5-羟色胺（5-HT），是由色氨酸衍生的主要胺。在果蝇中枢神经系统中大约有100个OA和5 HT神经元。在总OA池中，我们已经鉴定了一小组3或4个神经元，其共表达Fruitless的胺和雄性蛋白形式（FruM/OA神经元）。这些似乎参与了雄蝇在求爱和侵略之间做出的决定。在这里，我们建议使用最先进的遗传方法和组合方法来解开与FruM/OA神经元有关的电路，从感觉输入到行为输出。5 HT在果蝇的攻击性（不是发起战斗，而是将战斗带到更高的强度水平），求偶行为，平衡和进食行为中发挥作用。我们在这里要问的是，我们是否可以识别出参与这些行为的特定5 HT神经元，然后可以绘制出涉及与攻击有关的神经元或神经元的回路。该项目有以下具体目标：目标1：生成单个5 HT，OA和多巴胺（DA）神经元的形态特征和功能作用的数据库。目的2：选择性操纵FruM/OA神经元和行为选择：我们可以映射与这些神经元有关的电路。目的3：选择性操纵单个多巴胺能神经元。我们能不能确认。100个5 HT神经元与已知受5 HT影响的每个行为有关。如果是这样的话，我们是否可以像我们计划绘制FruM/OA电路一样，绘制与5 HT和攻击性有关的电路。在这个细节水平上探索胺神经元在行为中的作用的研究目前还不可能使用其他模型系统。 公共卫生关系：包括人类在内的所有生物都必须能够迅速评估社会状况，并从各种可能的行为选择中选择适当的反应。这种选择必须正确地进行，以使生物体作为个体或作为一个物种生存。生物体如何做出这样的选择，以及参与决策的潜在神经回路是如何构建的，是本应用程序的主题。