Mutant Studies of Aggression in Drosophila

描述(申请人提供)：攻击性是一种复杂的行为，表现在许多不同的社会背景中。这种行为经常被滥用，但对有机体的生存至关重要，人们对这种行为的生物学根源知之甚少。虽然模型系统可能不会复制攻击性的所有人类表现，但它们可以提供大量信息：基因、激素和经验在确定神经系统中的攻击性模式方面的相对重要性；详细描述涉及的神经回路；以及解决动物如何在其行为体系中可用的各种复杂行为中进行选择的问题。最后两个问题是本申请的主要焦点。近年来，克拉维茨实验室建立了果蝇攻击性模型，使这一重要行为可用于在高度适合遗传分析的有机体中进行实验分析。果蝇的攻击性是复杂的，雄蝇和雌蝇都表现出攻击性，动物从事许多其他相互关联的行为，可以对行为进行量化分析。然而，除此之外，基因组已经测序，而且有令人难以置信的强大方法，允许对果蝇进行实验操作，这在大多数其他动物模型系统中甚至还无法接近。最近，人们发现，决定谁会飞的基因也决定了苍蝇是像雄蝇还是雌蝇一样战斗。本申请扩展了这些研究，并有以下具体目标：i.通过绘制和操纵果蝇大脑的味觉中枢食道下神经节(SOG)内无果/双性相关的回路，探索果蝇在求爱和攻击之间的决策，这是果蝇行为的两种性别二态模式；ii.绘制与SOG回路相关的胺和多肽的受体的分布；以及iii.将基因引入神经元，这些基因可以改变这些神经细胞在动物身上的功能，并开始解决相同的神经元在雄性和雌性动物中的不同问题。这些研究使用了各种最先进的遗传学、行为学和解剖学方法来探索这些目的。例如，在与台湾蒋氏实验室的合作研究中，将绘制神经元图谱，以详细检查参与求爱和攻击的单个神经元之间的可能联系。重点将是以比现有水平高得多的分辨率来定义在攻击和求爱中重要的大脑回路，然后询问这种回路是如何在苍蝇的大脑中建立的，以及当冲突情况出现时，动物如何在行为反应之间做出选择。与公共卫生相关：包括人类在内的所有生物体都必须能够迅速评估社会状况，并从可能的各种可能行为选择中选择适当的反应。必须做出正确的选择，才能使生物体作为个体和物种得以生存。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是如何在神经系统中建立起来的，这些都没有被很好地理解，这也是这项应用的主题。

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.