Hormonal Modulation of Aggression in Drosophila

描述(申请人提供)：攻击性是群居动物行为的一种几乎普遍的特征，用于获取食物和住所、保护免受捕食和选择配偶。人们对这种行为背后的神经机制知之甚少，尽管大多数研究人员都认为神经激素在攻击性中起着重要作用。直到最近，人们还不知道在果蝇的普通实验室品系中存在打斗行为。随着基因组测序和丰富的遗传工具可用，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多肽在攻击中的作用。这款应用程序使用了一种简化的协议，允许在一对雄蝇和雌蝇之间看到可靠的战斗行为，这款应用有两个具体的目标。目的一、观察胺递质功能改变或释放对攻击行为的影响。为此，我们将：(I)使用经典的胺突变苍蝇品系；(Ii)使用GAL4/UAS系统来驱动苍蝇大脑含胺神经元中动力蛋白(参与突触小泡循环)的突变形式的表达，这种操作可以减少苍蝇在战斗时关闭胺神经元的可能性；以及(Iii)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。后两种操作现在对其他物种的动物是不可能的。我们还建议开始研究苍蝇大脑中的胺神经元回路。目的II.研究选择性干扰神经肽释放在神经元、共释放肽和经典递质化合物中的行为后果。为了实现这一目标，我们将：(I)使用质谱仪对苍蝇脑中的多肽进行鉴定和测序；(Ii)使用质谱仪与神经元标记相结合的方法来鉴定与胺和其他递质共存的多肽；以及(Iii)使用遗传工具选择性地干扰神经元肽的释放，并观察其对攻击的影响。相关性：人类社会中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。这些对果蝇的研究让人们得以独特地一瞥神经激素所起的作用，这是目前其他物种所没有的；比如已知在包括人类在内的所有动物物种的攻击性中起重要作用的胺和多肽。

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.