Hormonal Modulation of Aggression in Drosophila

描述(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，保护自己免受捕食和选择配偶。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性模型。在雄性和雌性果蝇的同性配对中，这些动物将争夺资源。男性发展等级关系，而女性不是，学习和记忆发生在男性打架的过程中。一个单一的基因，无果，既指定了苍蝇如何战斗，也指定了它们向谁求爱。到目前为止，在所有被检查的动物物种中，胺被证明在攻击中起着重要作用。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：去甲肾上腺素的苯酚类似物章鱼胺(OA)是从酪氨酸合成的主要胺；5羟色胺(5HT)是色氨酸的主要胺。果蝇中枢神经系统中约有100个OA和5HT神经元。在总的OA池中，我们已经确定了一小群3或4个神经元，它们共同表达无果(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爱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。5-羟色胺在果蝇的攻击性(不是发起打斗，而是使打斗达到更高的强度)、求偶行为、平衡和取食行为中发挥作用。我们在这里问，我们是否可以识别参与这些行为的特定5HT神经元，然后可以绘制涉及一个或多个与攻击有关的神经元的电路。该项目有以下具体目标：目标1：建立单个5-羟色胺、OA和多巴胺(DA)神经元的形态特征和功能角色的数据库。目的2：Frum/OA神经元的选择性操作和行为选择：我们能定位与这些神经元有关的回路吗？目的3：选择性操作单个5-羟色胺能神经元。我们能确定大约100个5-羟色胺神经元中的哪些与已知的受5-羟色胺影响的每种行为有关吗？如果是这样的话，我们是否可以像我们计划映射Frum/OA电路一样，映射与5HT和攻击性有关的电路。目前，在其他模型系统中还不可能在这种详细程度上探索胺神经元在行为中的作用。 公共卫生相关性：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，并从各种可能的行为选择中选择适当的反应。必须正确地做出这样的选择，以允许作为个体或作为一个物种的有机体的生存。生物体如何做出这样的选择，以及参与决策的潜在神经电路是如何构建的，是这一应用的主题。

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.