Hormonal Modulation of Aggression in Drosophila

果蝇攻击性的激素调节

基本信息

批准号：
7104477
负责人：
Edward A Kravitz
金额：
$ 32.63万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2010-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Aggression, a nearly universal feature of the behavior of social animals, is used for access to food and shelter, for protection from predation and for selection of mates. Little is known of the neural mechanisms that underlie the behavior, although most investigators agree that neurohormones play important roles in aggression. Until recently it was not well known that fighting behavior exists in common laboratory strains of the fruit fly, Drosophila melanogaster. With the genome sequenced and a wealth of genetic tools available, fruit flies can serve as a unique experimental model for the study of aggression. In this application, fruit flies will be used to examine the roles of amines and peptides in aggression. Using a simplified protocol that allows reliable fighting behavior to be seen between pairs of both male and female flies, this application has two Specific Aims. Aim I. To observe the behavioral consequences of altering amine transmitter function or release on aggression. Towards this goal, we will: (i) use classical amine mutant fly lines; (ii) use the GAL4/UAS system to drive the expression of a mutant form of the protein dynamin (involved in synaptic vesicle recycling) in amine-containing neurons in fly brains, a manipulation that alllows the turning off of amine neurons while flies are fighting; and (iii) use a newly developed method that allows the selective turning on of amine neurons while flies are fighting. The latter two manipulations are not now possible with other species of animals. We also propose beginning studies examining amine neuron circuitry in fly brains. Aim II. To examine the behavioral consequences of selectively interfering with neuropeptide release in neurons co-releasing peptides and classical transmitter compounds. Towards this goal we will: (i) use mass spectrometry to identify and sequence the peptides in fly brains; (ii) use mass spectrometry combined with labeling of neurons to identify peptides found co-localized with amines and other transmitters; and (iii) use genetic tools to selectively interfere with peptide release from neurons and observe the effects on aggression. Relevance: Violence in human society is a serious problem that must have a biological basis. Little is known, however, about the neuronal roots of aggression. These studies with fruit flies-allow unique glimpses, not available with other species at the present time, of the roles served by neurohormones;like amines and peptides that are known to be important in aggression in all species of animals, including man.

描述（由申请人提供）：攻击性是社会性动物行为的一个几乎普遍的特征，用于获取食物和住所、保护免受捕食和选择配偶。尽管大多数研究人员都认为神经激素在攻击行为中发挥着重要作用，但人们对这种行为背后的神经机制知之甚少。直到最近，人们还不知道常见的实验室果蝇品系（黑腹果蝇）中存在战斗行为。通过基因组测序和丰富的遗传工具，果蝇可以作为攻击性研究的独特实验模型。在此应用中，果蝇将用于检查胺和肽在攻击中的作用。该应用程序使用简化的协议，允许在雄性和雌性果蝇对之间看到可靠的战斗行为，有两个具体目标。目标 I. 观察改变胺递质功能或攻击性释放的行为后果。为了实现这一目标，我们将：（i）使用经典的胺突变体蝇系； (ii) 使用 GAL4/UAS 系统驱动果蝇大脑中含胺神经元中突变形式的蛋白质动力蛋白（参与突触小泡回收）的表达，这种操作允许在果蝇处于活动状态时关闭胺神经元。斗争; (iii) 使用一种新开发的方法，允许在果蝇战斗时选择性地打开胺神经元。后两种操作现在不适用于其他物种的动物。我们还建议开始研究检查果蝇大脑中的胺神经元回路。目标二。研究选择性干扰神经元共释放肽和经典递质化合物的神经肽释放的行为后果。为了实现这一目标，我们将：（i）使用质谱法来识别果蝇大脑中的肽并对其进行测序； (ii) 使用质谱法结合神经元标记来识别与胺和其他递质共定位的肽； (iii) 使用遗传工具选择性干扰神经元释放肽并观察对攻击性的影响。相关性：人类社会的暴力是一个严重的问题，必须有生物学基础。然而，人们对攻击性的神经元根源知之甚少。这些针对果蝇的研究可以让人们对神经激素所起的作用有独特的了解，这是目前其他物种所无法做到的；如已知的胺和肽，它们在包括人类在内的所有动物物种的攻击行为中发挥着重要作用。