Aggression in Drosophila: circuitry involved; learning and memory accompanying aggression; and establishing the circuitry of high-level aggression in the brain

果蝇的攻击性：涉及电路；

• 批准号: 9923698
• 负责人: Edward A Kravitz
• 金额: $ 58.17万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2021-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9923698
• 关键词: Address; Aggressive behavior; Animal Model; Animals; Behavior; Biological; Biological Models; Brain; Complex; Development; Dopamine; Drosophila genus; Food; Generations; Genetic; Heterogeneity; Human; Individual; Instinct; Learning; Memory; Modeling; Modernization; Nervous system structure; Neurons; Norepinephrine; Octopamine; Organism; Parents; Partner in relationship; Plant Roots; Reproducibility; Resources; Route; Science; Seeds; Series; Serotonin; Societies; Study models; System; Violence; Work; behavior measurement; bullying; dopaminergic neuron; fight against; fighting; fly; genetic manipulation; male; member; novel strategies; public health relevance; social; weapons

 DESCRIPTION (provided by applicant): Aggression is a normal innate behavior utilized for access to food, territory and mates by essentially all species of animals, including humans. Levels of display of aggression vary widely among individuals, however, and it generally is not known how much of this heterogeneity is genetic and how much is socially induced. Probably both mechanisms influence the expression of the behavior in all organisms, and the proportions of each that are involved vary widely between individuals. Unbridled aggression, in the form of violence, is a peculiarly human manifestation of this behavior, and when one adds the use of weapons capable of inflicting deadly damage to individuals and masses of individuals, it is a serious problem in society. Indeed weapons allow the least fit of individuals to become dominant protagonists in our society. In animal species, conspecifics sometimes kill opponents as well, but more commonly members of the same species engage in ritualistic stepwise-increasing-intensity-displays of fighting abilities. Winning and losing decisions can be made anywhere along the steps of such an intensity ladder. The roots of aggression are biological but there is little concrete information of how and where in the nervous system the seeds of violence are sown. In this application we propose to use a Drosophila model of aggression that we pioneered the use of in its modern form. Of all the available models for aggression, the Drosophila system offers the greatest ease and reproducibility of genetic manipulation within the nervous system down to single neuron levels. These manipulations can readily be combined with quantifiable behavioral measures in attempts to understand this complex behavior. Recently, using a novel strategy called intersectional genetics, we identified and manipulated in behaving animals single serotonin, dopamine and octopamine (fly equivalent of norepinephrine) neurons that all are involved in aggression. Thus, a single pair of serotonergic neurons found via this route, facilitat going to higher levels of aggression during fights, while a single pair of dopaminergic neurons are required to generate short term "winner" effects. In this application we ask a series of questions about the high-level aggression used by males to win fights. (1) What neurons and circuits are involved in going to high-intensity levels during fights, how do they work and how do they form during development? (2) What genetic or wiring differences exist in the nervous systems of the parent strain of flies and a hyper-aggressive line we generated called "bullies" that fight at higher intensity levels and always win fights against the parent strain? (3) Can we explain at cellular and circuit levels the learning and memory that takes place during fruit fly fights and accompanies the generation of "winner" and "loser" flies with changed aggression profiles? This application addresses the question of whether science and the study of model organisms can explain even a small part of the serious and pressing issues surrounding the root causes of human violence.

 描述（由申请人提供）：攻击性是一种正常的先天行为，几乎所有物种的动物（包括人类）都会利用攻击性来获取食物、领地和交配，但是，个体之间表现出攻击性的程度差异很大，而且通常不为人所知。这种异质性有多少是遗传的，有多少是社会引起的，这两种机制可能都会影响所有生物体的行为表达，而且个体之间所涉及的每种机制的比例差异很大。一个这种行为是人类特有的表现，当加上使用能够对个人和群体造成致命伤害的武器时，这就是社会上的一个严重问题。事实上，武器让最不健康的个人成为我们社会的主角。在动物物种中，同种动物有时也会杀死对手，但更常见的是，同一物种的成员会进行仪式性的逐步增加强度的战斗能力展示，可以在这种强度阶梯的任何地方做出输赢决定。攻击性的根源是生物学的，但关于暴力的种子如何以及在神经系统中的何处播种的具体信息很少。在本应用中，我们建议使用我们率先使用的现代形式的攻击性果蝇模型。在所有可用的攻击模型中，果蝇系统提供了神经系统内低至单个神经元水平的遗传操作的最大便利性和可重复性，这些操作可以很容易地与可量化的行为测量相结合，以试图理解这种复杂的行为。使用小说通过称为交叉遗传学的策略，我们在行为动物中识别并操纵了单个血清素、多巴胺和章多巴胺（果蝇相当于去甲肾上腺素）神经元，这些神经元都参与攻击行为，因此，通过这种途径发现的一对血清素能神经元有助于达到更高的水平。战斗期间的攻击性，而需要一对多巴胺能神经元来产生短期“获胜者”效应。在本应用中，我们提出了一系列有关高级的问题。雄性用来赢得战斗的攻击性。（1）在战斗中达到高强度水平涉及哪些神经元和电路，它们如何工作以及它们在发育过程中如何形成？果蝇亲本品系的神经系统和我们生成的称为“恶霸”的超攻击性品系，它们以更高的强度进行战斗，并且总是在与亲本品系的战斗中获胜（3）我们可以在细胞和电路水平上解释学习和记忆吗？发生在果蝇打架期间伴随着攻击行为发生变化的“赢家”和“输家”苍蝇的产生？该应用解决了科学和模式生物研究是否可以解释人类暴力根源的严重而紧迫的问题的一小部分的问题？ 。