The olfactory basis of locating nectar sugar sources in Aedes aegypti mosquitoes

埃及伊蚊定位花蜜糖源的嗅觉基础

• 批准号: 10207040
• 负责人: Omar Sultan Akbari
• 金额: $ 63.76万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-05 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10207040
• 关键词: Adult; Aedes; Affect; Anopheles Genus; Arboviruses; Behavior; Behavioral; Behavioral Assay; Biological Assay; Blood; Brain; CRISPR/Cas technology; Calcium; Chemicals; Culex (Genus); Culicidae; Data; Detection; Development; Discrimination; Disease; Drosophila genus; Effectiveness; Environment; Feeding behaviors; Female; Flowers; Flying body movement; Fruit; Gas Chromatography; Gene Targeting; Genes; Goals; Image; Immune response; Insect Vectors; Insecticides; Intervention; Ligands; Link; Lobe; Longevity; Mediating; Methods; Modeling; Mosquito Control; Neurons; Nutrient; Odorant Receptors; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Oocytes; Orphan; Outcome; Pathway interactions; Peripheral; Physiological Processes; Plants; Play; Population; Process; Publishing; Rapid screening; Reproduction; Role; Shapes; Smell Perception; Source; Surveys; System; Technology; Testing; Variant; Vectorial capacity; Work; base; behavior test; comparative; contrast enhanced; experimental study; feeding; gamma-Aminobutyric Acid; genetic approach; genome editing; insight; male; mutant; mutualism; programs; relating to nervous system; response; sugar; tool; vector management strategies; vector mosquito

The objective of the proposed R01 project is to build on our recent findings that attractive odors from sources of nectar activate conserved olfactory channels in mosquitoes, and the odorant ratios within the scent, along with the inhibition in the antennal lobe (AL), are critical for Aedes aegypti behavior. Feeding on fruits and flowers is a vital behavior for mosquitoes, and mosquito attraction to these sources of nectar is mediated by the ratio of key odorants in the bouquet. Bait-and-kill traps that use fruit syrups have effectively controlled local mosquito populations, but variation in the fruit odor can strongly impact its attractiveness. We still have not identified the odor constituents and ratios that are attractive in the nectar odors – enabling the development of synthetic lures –, nor how this information is detected and processed by the mosquito's olfactory system. Nectar-feeding by female mosquitoes increases their life-span and decreases the gonotrophic cycle, thereby increasing their vectorial capacity, and for adult males, it is the only source of nutrients. Our recent work allowed us to identify the odor constituents that mediate nectar-feeding behaviors in Ae. aegypti and understand how the odor is processed in the brain. Now in this application, we propose to use a combination of behavioral assays, chemical methods combined with calcium imaging in tethered flying mosquitoes, and genetic approaches to study the olfactory basis of nectar-seeking behaviors. Aim 1 will allow us to identify attractive odorants in the scents of diverse plant nectar sources and use heterologous expression systems to de-orphan the cognate odorant receptors (Ors). We also take advantage of the Q-system for genetically characterizing three Ors (Or15, Or49, and Or2) that are essential for representing the proper ratios in nectar odors. In Aim 2, we leverage our existing and new GCaMP expression lines to examine how the ratios of these key odorants are processed in the AL, and how GABAergic inhibition shapes these responses. In Aim 3, we will use our identified odor lures, and artificial lures that vary in their natural ratios of key odorants, to determine their efficacy in bait-and-kill systems. Together, these experiments will test the working hypothesis that nectar odors and their specific odorant ratios activate conserved olfactory channels to be processed similarly by AL circuits to mediate feeding behaviors. While there has been an extensive study of mosquito attraction to blood hosts, we know comparatively less about nectar feeding. Our experiments will identify new odors that can be immediately deployed as attractant lures. Additionally, GABAergic systems are involved in diverse physiological processes in insect vectors, including olfaction, immune response, and arbovirus replication, as well as being potent targets for insecticides. Generating mutants that target the mosquito's olfactory responses or GABAergic pathways could provide additional insight into these diverse processes. Sugar feeding plays an essential role in the vectorial capacity of mosquitoes and the spread of diseases that afflict over a billion people annually. Therefore, unraveling the neural bases of nectar-feeding will enable new gene-targets and tools for their control.

拟议的R01项目的目的是基于我们最近的发现，即来自 花蜜激活蚊子中的嗅觉通道，而恐怖中的气形比 触角叶（Al）的抑制作用对于伊德斯埃及行为至关重要。以水果和鲜花为食 蚊子的至关重要行为以及对这些花蜜来源的蚊子吸引力是由比率介导的 花束中的关键气味。使用水果sylp的诱饵和杀伤陷阱有效控制了当地蚊子 人群，但是果味的变化会严重影响其吸引力。我们仍然没有确定 气味构成在花蜜气味中具有吸引力的比率 - 使合成诱饵的发展 - ，也没有蚊子的嗅觉系统如何检测和处理这些信息。 雌性蚊子的花蜜喂养会增加寿命并减少贡献循环，从而增加寿命 增加了其矢量能力，对于成年男性，它是唯一的营养来源。我们最近的工作允许 我们确定介导AE中介导花蜜喂养行为的气味构成的气味。埃及，了解 气味在大脑中加工。现在，在此应用程序中，我们建议使用各种行为测定的组合， 化学方法与束缚飞行蚊子中的钙成像结合在一起，遗传方法 研究寻求花蜜行为的嗅觉基础。 AIM 1将使我们能够在 潜水员植物花蜜来源的气味并使用异源表达系统去除孔子 气压受体（OR）。我们还利用Q系统来遗传表征三个OR（OR15，， OR49，OR2）对于表示花蜜气味中适当比率至关重要。在AIM 2中，我们利用我们的 现有和新的GCAMP表达线，以检查如何处理这些关键气味的比率 Al，以及GABA能抑制如何塑造这些反应。在AIM 3中，我们将使用我们确定的气味诱饵，并使用 人工诱饵的自然气味比例不同，以确定其在诱饵系统中的效率。 这些实验将共同测试蜜蜂气味及其特定气味比的工作假设 激活组成的嗅觉通道，以类似的方式通过Al电路处理以介导喂养行为。 尽管对蚊子吸引血液宿主的吸引力进行了广泛的研究，但我们知道相对较少 关于花蜜喂养。我们的实验将确定可以立即部署为吸引剂的新气味 诱饵。此外，GABA能系统参与了昆虫载体的潜水物理过程， 包括嗅觉，免疫反应和arbovirus复制，以及杀虫剂的潜在靶标。 生成针对蚊子的嗅觉反应或GABA能途径的突变体可以提供 对这些潜水过程的进一步见解。糖喂食在矢量能力中起着至关重要的作用 蚊子和每年遭受十亿人口的疾病的传播。因此，揭开 花蜜喂养的神经基础将使新的基因目标及其控制。