Hormonal Modulation of Aggression in Drosophila

描述（由申请人提供）：攻击性是一种与生俱来的行为，几乎是动物社会行为的普遍特征。在野外，它被用来获取食物和住所，保护自己不被捕食，以及选择配偶。尽管它很重要，但人们对这种行为背后的神经机制知之甚少。在过去的十年里，我们开发了一个黑腹果蝇的攻击模型。在雄性和雌性果蝇的同性配对中，这些动物会争夺资源。雄性发展了等级关系，而雌性没有，学习和记忆发生在雄性打架的过程中。一个没有结果的单一基因决定了苍蝇如何战斗以及它们向谁求爱。到目前为止，在所有被研究的动物物种中，胺类都被证明在攻击行为中起着重要作用。果蝇也不例外。这些研究集中在果蝇神经系统中发现的两种主要胺：章鱼胺（OA），去甲肾上腺素的酚类似物，是由酪氨酸合成的主要胺；5 -羟色胺（5HT）是由色氨酸衍生的主要胺。果蝇中枢神经系统中约有100个OA和5HT神经元。在整个OA池中，我们已经确定了一小组3或4个神经元，它们共同表达了无果性（FruM/OA神经元）的胺和雄性蛋白形式。这些似乎与雄性果蝇在求偶和攻击之间做出的决定有关。在这里，我们建议使用最先进的遗传方法和组合方法来解开与FruM/OA神经元有关的电路，从感觉输入到行为输出。5HT在苍蝇的攻击行为（不是发起战斗，而是使战斗达到更高的强度）、求偶行为、平衡和摄食行为中起作用。我们的问题是，我们能否识别出参与这些行为的特定5HT神经元，然后绘制出与攻击有关的神经元或神经元的电路。该项目有以下具体目标：目标1：生成单个5HT、OA和多巴胺（DA）神经元的形态特征和功能作用的数据库。目的2：选择性操纵FruM/OA神经元和行为选择：我们能否绘制与这些神经元有关的电路？目的3：选择性操纵单个血清素能神经元。我们能否在大约100个5HT神经元中确定哪些神经元与已知受5HT影响的每种行为有关？如果是这样，我们是否可以绘制与5HT和攻击性相关的电路，就像我们计划绘制FruM/OA电路一样。在目前的其他模型系统中，探索胺神经元在行为中的作用在这种细节水平上的研究是不可能的。

DESCRIPTION (provided by applicant): Aggression is an innate behavior that is a nearly universal feature of the social behavior of animals. In the wild, it is used for access to food and shelter, for protection from predation and for selection of mates. Despite its importance little is known of the neural mechanisms that underlie the behavior. Over the past decade, we have developed a Drosophila melanogaster model of aggression. In same sex pairing of male and female flies, these animals will compete over resources. Males develop hierarchical relationships while females do not, and learning and memory take place during the male fights. A single gene, fruitless, specifies both how flies fight and who they court. Amines have been shown to be important in aggression in all species of animals examined thus far. Fruit flies are no exception. These studies focus on two major amines found in the fruit fly nervous system: octopamine (OA), the phenol analogue of norepinephrine, is the major amine synthesized from tyrosine; and serotonin (5HT), is the major amine derived from tryptophan. There are approximately 100 OA and 5HT neurons in the Drosophila central nervous system. Of the total OA pool, we have identified a small group of 3 or 4 neurons, that co-express the amine and the male protein forms of Fruitless (FruM/OA neurons). These appear to be involved in the decision made by male flies between courtship and aggression. Here we propose to use state of the art genetic methods and a combinatorial method to unravel the circuitry concerned with the FruM/OA neurons, from sensory input through to behavioral output. 5HT serve roles in aggression (not in initiating fights, but in bringing fights to higher intensity levels), courtship behavior, balance and feeding behavior in flies. We ask here whether we can identify the specific 5HT neurons involved in these behaviors, and then can map the circuitry involving the neuron or neurons concerned with aggression. The project has the following Specific Aims: Aim 1: To generate a data base of the morphological features and functional roles served by individual 5HT, OA and dopamine (DA) neurons. Aim 2: Selective manipulation of FruM/OA neurons and behavioral choice: can we map the circuitry concerned with these neurons. Aim 3: Selective manipulation of individual serotonergic neurons. Can we identify which of the ca. 100 5HT neurons are concerned with each of the behaviors known to be influenced by 5HT? If so, can we then map the circuitry involved with 5HT and aggression, the same way we plan to map the FruM/OA circuitry. Studies exploring the roles of amine neurons in behavior at this level of detail just are not possible with other model systems at the present time. PUBLIC HEALTH RELEVANCE: All organisms, including humans, must be capable of rapidly evaluating social situations and of selecting proper responses from a wide variety of possible behavioral choices. Such selections must be correctly made to allow the survival of organisms as individuals or as a species. How organisms make such choices and how the underlying neural circuitry involved in decision making is constructed are the themes of this application.