Role of the T1 Neuronal Circuit in Pheromone Behaviors

描述(由申请人提供)：T1神经元回路在信息素行为中的作用研究综述了解行为的分子和细胞基础是非常重要的，这对于了解行为背后的底物的学术兴趣，以及理解人类行为和精神疾病的潜在临床相关性都是非常重要的。我们建议在一个遗传上容易处理的动物模型系统中研究一个简单的行为范式：挥发性信息素触发的黑腹果蝇行为。11-顺式痘苗烯基乙酸酯(CVA)是一种雄性产生的信息素，调节果蝇的聚集和性行为。CVA的检测是通过位于触角上毛状感受器上的少量嗅觉神经元进行的。毛状感受器(T1感受器)的一个子集内的神经元精细地调节到CVA，似乎是CVA的主要感知途径。然而，最近的工作也表明，在CVA介导的行为和学习中，有一组不同的毛状神经元表达Or65a。为了开始剖析这两条通路在CVA诱导的行为中的作用，我们将检查T1通路的缺失或结构性激活对行为的影响。我们提出了两个具体目标。首先，我们将创造一种表达细胞外信息素结合蛋白LUSH的显性、激活变体的苍蝇，这将使我们能够操纵神经元回路中的活动。其次，我们将使用表达激活的LUSH或T1活性降低的突变体的果蝇来剖析T1回路中活性增加或减少对行为的作用。这些研究的结果将为T1神经元回路在CVA诱导行为中的作用提供新的见解。与公共健康相关的信息素会在动物身上引发遗传上固有的社会行为，如繁殖和攻击。在昆虫中，信息素引导交配行为和聚集到食物来源。因此，了解昆虫神经系统是如何感知和解码信息素的，对于控制传播疾病或破坏农业的昆虫具有很大的实用价值。我们研究果蝇体内的信息素信号，在那里我们可以将遗传分析应用于行为。信息素CVA对果蝇的交配和聚集很重要，它似乎是通过两个不同的神经元回路来感觉的。在这里，我们将使用基因操作来激活或停用这些途径，以阐明每个途径对交配和聚集行为的行为贡献。这些研究的预期结果将帮助我们了解昆虫对信息素的感知是如何发生的。

DESCRIPTION (provided by applicant): The role of the T1 neuronal circuit in pheromone behaviors Research Summary Understanding the molecular and cellular basis of behavior is of great importance, both for the academic interest of understanding the substrates underlying behavior, and for the potential clinical relevance of understanding human behavior and mental illness. We propose to study a simple behavior paradigm in a genetically tractable animal model system; volatile pheromone-triggered behaviors in Drosophila melanogaster. 11-cis- vaccenyl acetate (cVA) is a male-produced pheromone that mediates aggregation and sexual behavior in Drosophila. cVA detection occurs through a small number of olfactory neurons located in trichoid sensilla on the antenna. Neurons within a subset of trichoid sensilla (the T1 sensilla) are exquisitely tuned to cVA and appear to be the primary cVA perception pathway. However, recent work also implicates a distinct set of trichoid neurons expressing Or65a in cVA-mediated behavior and learning. To begin to dissect the contribution of these two pathways in cVA-induced behavior, we will examine the effect of the loss or the constitutive activation of the T1 pathway on behavior. We propose two specific aims. First, we will create flies expressing a dominant, activating variant of the extracellular pheromone-binding protein LUSH that will allow us to manipulate the activity in this neuronal circuit. Second, we will use flies expressing activated LUSH or mutants with reduced T1 activity to dissect the role of increased or decreased activity in the T1 circuit on behavior. The results of these studies will provide new insights into the role of the T1 neuronal circuit in cVA-induced behavior. PUBLIC HEALTH RELEVANCE Pheromones trigger social behaviors in animals that are genetically hard wired, such as reproduction and aggression. In insects, pheromones guide mating behavior and aggregation to food sources. Therefore, understanding how pheromones are perceived and decoded by the insect nervous system could be of great practical benefit to control insects that transmit diseases or destroy agriculture. We study pheromone signaling in the Drosophila, where we can apply genetic analysis to behavior. The pheromone cVA is important for mating and aggregation in fruit flies, and appears to be sensed through two different neuronal circuits. Here, we will use genetic manipulations to activate or inactivate these pathways to elucidate the behavioral contributions of each to mating and aggregation behaviors. The expected results from these studies will help us understand how pheromone perception occurs in insects in general.