Mutant Studies of Aggression in Drosophila

描述（由申请人提供）：攻击是一种复杂的行为，在许多不同的社会背景下表达。经常被滥用，但对生物体的生存至关重要，很少有人知道这种行为的生物学根源。虽然模型系统可能无法复制人类表现的所有攻击行为，但它们可以提供大量信息：基因、激素和经验在神经系统中制定攻击模式的相对重要性;详细描述所涉及的神经回路;以及解决动物如何在其行为库中选择各种复杂行为的问题。最后两个问题是本申请的主要焦点。近年来，Kravitz实验室建立了一个果蝇攻击模型，使这种重要的行为可用于高度适合遗传分析的生物体的实验分析。果蝇的攻击行为是复杂的，雄性和雌性都表现出攻击行为，动物从事许多其他相互关联的行为，并且这些行为可以定量分析。然而，除此之外，基因组已经被测序，并且有非常强大的方法可以使用果蝇进行实验操作，这些方法甚至不能在大多数其他动物模型系统中进行近似。最近，人们发现，决定谁会向谁求爱的同一个基因也决定了苍蝇是像雄性还是雌性那样打架。本申请扩展了这些研究，并且具有以下具体目的：探索求偶和攻击之间的决策，两种性二态行为模式的苍蝇，通过映射和操纵的无果/doublesex相关的电路在食管下神经节（SOG），果蝇大脑的味觉中心; II。绘制与SOG电路相关的胺和肽的受体分布;和III.将基因导入神经元，改变动物行为中这些神经细胞的功能，并开始解决雄性和雌性动物中相同神经元的差异问题。这些研究使用各种最先进的遗传学、行为学和解剖学方法来探索这些目标。例如，在与台湾蒋实验室的合作研究中，将制作神经元地图，以便详细检查涉及求爱和攻击的单个神经元之间的可能联系。重点将是在比现在更高的分辨率水平上定义在攻击和求爱中重要的大脑回路，然后询问该回路如何在苍蝇大脑中建立，以及当冲突情况出现时动物如何在行为反应之间进行选择。公共卫生相关性：包括人类在内的所有生物都必须能够迅速评估社会状况，并从各种可能的行为选择中选择适当的反应。这种选择必须正确地进行，以使生物体既作为个体又作为物种生存。生物体如何做出这样的选择，以及极其复杂的先天行为模式如何在神经系统中建立起来，这些都还没有得到很好的理解，这也是本申请的主题。

DESCRIPTION (provided by applicant): Aggression is a complex behavior expressed in many different social contexts. Often abused, yet essential for the survival of organisms, little is known of the biological roots of this behavior. While model systems may not duplicate aggression in all of its many human manifestations, they can be highly informative about: the relative importance of genes, hormones and experience in laying down patterns of aggression in nervous systems; detailing the neural circuitry involved; and addressing questions of how animals choose among the varied complex behaviors available within their behavioral repertoires. It is the last two matters that are the major focus of the present application. In recent years, the Kravitz laboratory has established a fruit fly model of aggression making this important behavior available for experimental analysis in an organism that is highly suitable for genetic analysis. With fruit flies aggression is complex and is shown by both males and females, the animals engage in many other inter-related behaviors, and the behaviors can be quantitatively analyzed. In addition, however, the genome has been sequenced and incredibly powerful methods are available that allow experimental manipulations to be performed with fruit flies that cannot yet even be approximated in most other animal model systems. Recently, it has been found that the same gene that determines who flies court also determines whether flies fight like males or females. The present application extends these studies and has the following Specific Aims: I. To explore decision-making between courtship and aggression, two sexually dimorphic patterns of behavior in flies, by mapping and manipulating the fruitless/doublesex-associated circuitry within the subesophageal ganglion (SOG), the taste center in fruit fly brains; II. To map the distribution of receptors for amines and peptides associated with the SOG circuitry; and III. To introduce genes into neurons that can alter the function of these nerve cells in behaving animals and to begin to address the question of how the same neurons differ in male and female animals. These studies use a wide variety of state-of-the-art genetic, behavioral and anatomical methods in exploring these Aims. For example, in collaborative studies with the Chiang laboratory in Taiwan, neuronal maps will be made that will allow examination in great detail of the possible connections between individual neurons involved in courtship and aggression. The focus will be to define the brain circuitry important in aggression and courtship at much higher levels of resolution than are now available, and then to ask how that circuitry gets established in fly brains and how animals choose between behavioral responses when conflict situations arise. PUBLIC HEALTH RELEVANCE: All organisms, including humans, must be capable of rapidly evaluating social situations and selecting proper responses from what may be a wide variety of possible behavioral choices. Such selections must be made correctly in order to allow the survival of organisms both as individuals and as species. How organisms make such choices and how patterns of innate behavior of great complexity get established in nervous systems are not well understood, and are the theme of this application.