From Pheromone Receptors to Social Behaviors

描述(由申请人提供)：我们的长期目标是阐明具有复杂神经系统的动物的普遍特征--社会行为是如何通过有机体的各种感觉系统受到遗传控制的。作为一般策略，我们将以果蝇为模型系统来阐明信息素及其受体在社会行为中的作用，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的识别在这些行为中起着核心作用。在果蝇和其他昆虫中，由嗅觉(Or)和味觉受体(Gr)基因编码的两个七跨膜受体家族的成员被认为识别信息素。对这些受体的刺激会激活中枢神经系统中的神经丛，这些神经丛被认为也接受来自其他感觉形式(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觉通道的信息，并控制个体之间在求爱、攻击性和其他社会互动过程中精心设计的行为表现。了解这种复杂的集成电路是如何运作的，是现代分子神经生物学的主要科学挑战之一。我们之前已经发现了一种真正的信息素受体，它在雄性求爱过程中发挥着重要作用。该受体由GR亚家族成员Gr68a编码，包括其他5个GR基因-Gr32a、Gr39a.a、Gr39a.b、Gr39a.c和Gr39a.d。我们建议的中心假设是，所有这些Gr基因都编码信息素受体，在果蝇的不同社会行为中具有特定的作用。我们将采用反向遗传学的方法来阐明这些受体的作用。我们将为所有6个Gr信息素受体基因产生敲除等位基因，产生Gr突变果蝇品系，并对这些果蝇进行广泛的行为分析，以阐明Gr基因在求偶激活、求爱抑制、攻击、吸引雌性和其他社会行为中的功能。我们将绘制GR表达、信息素敏感神经元的轴突投射图，并识别与其轴突形成突触的神经元目标。最后，我们将确定这些GR信息素受体识别的主要化合物，从而代表激活这些神经回路的线索。与公共健康相关：这项拨款将以果蝇为模型系统，研究信息素受体在包括性行为、攻击和拒绝在内的复杂社会行为中的具体作用。拟议的研究将使用广泛的遗传分析、行为实验和神经解剖学研究来确定这些受体的功能，目的是揭示受体和行为之间的联系。我们的工作将极大地扩展我们对信息素引导的复杂行为和控制它们的神经回路的相当贫乏的知识，这是行为和分子神经科学领域的一个热门话题。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.