From Pheromone Receptors to Social Behaviors

我们的长期目标是阐明社会行为， 具有复杂神经系统的动物，通过各种感官控制基因 有机体中的系统。作为一般策略，我们将利用黑腹果蝇作为 模型系统阐明信息素及其受体在社会行为中的作用， 例如求偶、交配、攻击等。在大多数哺乳动物和昆虫中， 接触和/或挥发性信息素信号在这些行为中起中心作用。果蝇 和其他昆虫，两个七跨膜受体家族的成员，由 嗅觉（Or）和味觉受体（Gr）基因被认为识别信息素。 这些受体的刺激导致中枢神经系统中神经系综的激活， 被认为还接收来自其他感觉模态（即视觉和听觉）的输入。 最后，一个复杂的神经回路必须整合来自这些不同感官的信息， 渠道和控制在求爱，侵略和其他精心的行为显示 个人之间的社会互动。为了了解如此复杂的集成电路 操作是现代分子神经生物学的主要科学挑战之一。 我们以前已经确定了一个真正的信息素受体，它起着主要的作用。 在男性求爱中的作用该受体由Gr亚家族的成员Gr 68 a编码， 包括另外五个Gr基因-Gr 32a、Gr39a.a、Gr39a.b、Gr39a.c和Gr39a.d。中央 我们提出的假设是，所有这些Gr基因编码信息素受体， 在果蝇不同的社会行为中扮演着特殊的角色。我们将进行反向遗传 方法来阐明这些受体的作用。我们会把这六个基因的等位基因都敲除 Gr信息素受体基因，产生Gr突变蝇株并进行广泛的 对这些果蝇进行行为分析以阐明Gr基因在求偶激活中的功能， 求偶抑制、攻击、女性吸引和其他社会行为。我们要绘制地图 GR表达、信息素感受神经元轴突投射和鉴定的神经元 与轴突形成突触的靶点。最后，我们将确定主要的化学物质 由这些GR信息素受体识别的化合物，因此，代表 激活这些神经回路的线索这项拨款将研究信息素受体在复杂的 社会行为，包括性行为，攻击和拒绝，使用 果蝇作为一个模型系统。拟议的研究将采用广泛的 遗传分析、行为实验和神经解剖学研究， 确定这些受体的功能，目的是揭示 受体和行为。我们的工作将大大扩大我们相当贫穷的 信息素引导的复杂行为和神经回路的知识， 控制它们，这是行为和分子神经科学领域的一个热门话题。

Our long-term objective is to elucidate how social behaviors, universal features of animals with complex nervous systems, are genetically controlled through the various sensory systems in an organism. As a general strategy, we will utilize Drosophila melanogaster as a model system to elucidate the roles of pheromones and their receptors in social behaviors, such as courtship, mating, aggression etc. In most mammals and insects, the recognition of contact and/or volatile pheromone signals plays a central role in these behaviors. In Drosophila and other insects, members of two families of seven-transmembrane receptors, encoded by the olfactory (Or) and gustatory receptor (Gr) genes, are thought to recognize pheromones. Stimulation of these receptors leads to the activation of neural ensembles in the CNS, which are thought to receive also input from other sensory modalities (i.e. visual and auditory). Finally, a complex neural circuit must integrate the information from these diverse sensory channels and control the elaborate behavioral displays during courtship, aggression and other social interactions between individuals. To understand how such complex, integrated circuits operate is one of the main scientific challenges in modern, molecular neurobiology. We have previously identified a bona fide pheromone receptor, which plays a major role in male courtship. This receptor is encoded by Gr68a, a member of a Gr subfamily, which includes five other Gr genes - Gr32a, Gr39a.a, Gr39a.b, Gr39a.c and Gr39a.d. The central hypothesis of our proposal is that all these Gr genes encode pheromone receptors with specific roles in diverse social behaviors in Drosophila. We shall take a reverse genetic approach to elucidate the roles of these receptors. We will generate knock-out alleles for all six Gr pheromone receptor genes, generate Gr mutant fly strains and perform extensive behavioral analyses with these flies to elucidate Gr gene functions in courtship activation, courtship suppression, aggression, female attraction and other social behaviors. We shall map the axonal projections of Gr-expressing, pheromone-sensing neurons and identify neuronal targets that form synapses with their axons. Finally, we shall identify the main chemical compounds that are recognized by these GR pheromone receptors, and hence, represent the cues that activate these neural circuits. This grant will investigate the specific role of pheromone receptors in complex social behaviors including sexual behavior, aggression and rejection, using the Drosophila as a model system. The proposed studies will employ extensive genetic analyses, behavioral experiments and neuroanatomical investigations to identify the function of these receptors, with the goal to reveal links between receptors and behavior. Our work will significantly expand our rather poor knowledge of pheromone-guided complex behavior and neural circuits that control them, a hot topic in the field of behavioral and molecular neuroscience.