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；

基本信息

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
项目类别：
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

项目摘要

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（适用提供）：侵略是一种正常的先天行为，用于通过包括人类在内的所有动物，用于进入食物，领土和伴侣。然而，侵略性的表现水平差异很大，而且通常不知道这种异质性是遗传性的多少以及社会诱导了多少。这两种机制可能都会影响所有生物体中行为的表达，并且每个生物的特性在个体之间差异很大。以暴力的形式，无限的侵略性是这种行为的特殊人类表现，当人们添加使用能够对个人和个人造成致命损害的武器时，这是社会上的一个严重问题。在动物物种中，考虑因素有时也会杀死选择，但更常见的是同一物种的成员参与战斗能力的仪式性逐步增强强度划分。可以沿着这种强度梯子的步骤做出胜利和失败的决定。侵略性的根源是生物学的，但几乎没有关于神经系统如何以及在哪里播种的混凝土信息。在此应用程序中，我们建议使用果蝇模型的侵略性模型，我们以现代形式开创了使用。在所有可用的侵略性模型中，果蝇系统在神经系统内提供了最大的遗传操纵，以至于单个神经元水平。这些操作可以轻松地与可量化的行为度量相结合，以了解这种复杂的行为。最近，使用一种称为交叉遗传学的新型策略，我们在行为动物中识别和操纵单一5-羟色胺，多巴胺和章鱼胺（Fly等于（1）（1）在战斗过程中涉及哪些神经元和电路在高强度上涉及高强度，它们在发育过程中如何工作以及它们在发育中如何形成？称为“欺凌者”，在较高的强度水平上战斗，并始终与父母的压力打架？