From Pheromone Receptors to Social Behaviors

我们的长期目标是阐明人类的社会行为、普遍特征 拥有复杂神经系统的动物，通过不同的感官受到基因控制 生物体中的系统。作为一个总体策略，我们将利用果蝇作为一种 阐明信息素及其受体在社会行为中的作用的模型系统， 如求偶、交配、攻击等。在大多数哺乳动物和昆虫中，对 接触和/或挥发性信息素信号在这些行为中起着核心作用。在果蝇中 和其他昆虫，属于两个七跨膜受体家族的成员，由 嗅觉(或)和味觉受体(Gr)基因被认为识别信息素。 刺激这些受体导致中枢神经系统神经丛的激活，这是 被认为也接受来自其他感官形式(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。 引导和控制求爱、攻击等过程中精心设计的行为表现 个人之间的社会互动。为了理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。 我们之前已经确定了一种真正的信息素受体，它扮演着主要的 在男性求爱中扮演的角色。该受体由Gr亚家族成员Gr68a编码，Gr亚家族成员 包括其他五个GR基因-Gr32a、Gr39a.a、Gr39a.b、Gr39a.c和Gr39a.d。中环 我们提出的假设是，所有这些Gr基因都编码信息素受体 果蝇在不同社会行为中的特定角色。我们将采取反向基因 阐明这些受体的作用的方法。我们将为所有六个人产生敲除等位基因 GR信息素受体基因，产生GR突变苍蝇品系并广泛执行 对这些苍蝇进行行为分析以阐明GR基因在求偶激活中的功能， 压抑求爱、侵犯女性、吸引女性等社会行为。我们将绘制地图 生长激素受体表达、信息素敏感神经元的轴突投射及其识别 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信号。这项资助将调查信息素受体在复合体中的具体作用。 社交行为，包括性行为、攻击性和拒绝，使用 以果蝇为模型系统。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，目的是揭示它们之间的联系 受体和行为。我们的工作将极大地扩大我们相当贫穷的人 信息素引导的复杂行为和神经回路的知识 控制他们，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.