Hormonal Modulation of Aggression in Drosophila

果蝇攻击性的激素调节

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7104477
• 关键词: Drosophilidae; aggression; amines; arthropod genetics; behavioral genetics; brain; dynamin; ethology; genetic models; genetic regulation; genetic strain; hormone regulation /control mechanism; mass spectrometry; neuroanatomy; neurogenetics; neurohormones; neurons; neuropeptides; neuroregulation; neurotransmitters; peptides; protein localization; protein sequence; synaptic vesicles; violence

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，保护自己免受捕食者的侵害，以及选择配偶。尽管大多数研究人员都认为神经激素在攻击行为中起着重要作用，但人们对这种行为背后的神经机制知之甚少。直到最近，人们才知道，在实验室中常见的果蝇——黑腹果蝇——中是否存在打斗行为。随着基因组测序和丰富的遗传工具的可用性，果蝇可以作为研究攻击性的独特实验模型。在这项应用中，果蝇将被用来研究胺和肽在攻击中的作用。使用一种简化的协议，可以看到雄性和雌性苍蝇之间可靠的战斗行为，这个应用程序有两个特定的目的。目的一：观察改变胺递质功能或释放对攻击行为的影响。为了实现这一目标，我们将：(i)使用经典胺突变蝇系；（ii）使用GAL4/UAS系统驱动果蝇大脑中含胺神经元中蛋白质动力蛋白（参与突触囊泡循环）突变形式的表达，这种操作允许在果蝇战斗时关闭胺神经元；（三）使用一种新开发的方法，允许在苍蝇战斗时选择性地打开胺神经元。后两种操作现在在其他种类的动物身上是不可能的。我们还建议开始研究苍蝇大脑中的胺神经元回路。目的二世。研究选择性干扰神经肽释放对神经元共释放肽和经典递质化合物的行为后果。为了实现这一目标，我们将：(i)使用质谱法鉴定和测序苍蝇大脑中的肽；（ii）使用质谱结合标记神经元来鉴定与胺和其他递质共定位的肽；（三）利用遗传工具选择性地干扰神经元的肽释放，观察对攻击性的影响。相关性：人类社会中的暴力是一个必须有生物学基础的严重问题。然而，我们对攻击性的神经元根源知之甚少。这些以果蝇为研究对象的研究，让我们对神经激素所起的作用有了独特的了解，这在目前的其他物种中是不可能的；比如胺和多肽，它们在包括人类在内的所有动物的攻击性中都起着重要作用。