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: 10582687
• 负责人: Omar Sultan Akbari
• 金额: $ 63.63万
• 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/10582687
• 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; Persons; Physiological Processes; Plants; Play; Population; Process; Publishing; Rapid screening; Reproduction; Role; Shapes; Smell Perception; Source; Surveys; System; Technology; Testing; Variant; Vectorial capacity; Volatilization; Work; base; behavior test; comparative; contrast enhanced; experimental study; feeding; gamma-Aminobutyric Acid; genetic approach; genome editing; insight; male; mutant; mutualism; neural; programs; response; sugar; tool; vector management strategies

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.

建议的R01项目的目标是基于我们最近的发现，来自 花蜜激活蚊子保守的嗅觉通道，气味中的气味比率，以及 触角叶(AL)的抑制对埃及伊蚊的行为是至关重要的。以水果和鲜花为食 蚊子的一种重要行为，蚊子对这些花蜜来源的吸引是由 花束中的关键香料。使用水果糖浆的诱杀陷阱有效地控制了当地的蚊子 但水果气味的变化会极大地影响其吸引力。我们还没有确定 花蜜气味中诱人的气味成分和比例--使合成诱饵的开发成为可能 -，也不知道蚊子的嗅觉系统是如何检测和处理这些信息的。 雌性蚊子以花蜜为食可延长寿命，缩短生殖周期，从而 增加它们的媒介能力，对于成年雄性来说，这是唯一的营养来源。我们最近的工作允许 美国以确定介导白蚁采蜜行为的气味成分。并理解埃及人是如何 气味是在大脑中处理的。现在在这个应用程序中，我们建议使用行为分析的组合， 结合钙成像的化学方法和遗传方法对被拴住的飞蚊进行研究 研究寻蜜行为的嗅觉基础。AIM 1将使我们能够识别出 不同植物花蜜来源的气味，并使用异源表达系统使同源基因去孤儿 气味受体(ORS)。我们还利用Q系统对三个Ors(或15， 49和2)，这对于代表花蜜气味中的适当比例是必不可少的。在目标2中，我们利用我们的 现有的和新的GCaMP表达式行，以检查这些关键气味的比例是如何在 Al，以及GABA能抑制如何塑造这些反应。在目标3中，我们将使用我们识别的气味诱饵，以及 人工诱饵在关键气味物质中的自然比例不同，以确定其在诱杀系统中的效果。 总之，这些实验将检验工作假设，即花蜜气味及其特定的气味比例 激活保守的嗅觉通道，由AL电路进行类似的处理，以调节摄食行为。 虽然对蚊子对血液宿主的吸引力进行了广泛的研究，但我们知道的相对较少。 关于喂花蜜的事。我们的实验将识别出可以立即用作引诱剂的新气味 诱饵。此外，GABA能系统参与昆虫媒介的不同生理过程， 包括嗅觉、免疫反应和虫媒病毒复制，以及作为杀虫剂的有效靶标。 产生针对蚊子的嗅觉反应或GABA能途径的突变体可以提供 对这些不同流程的更多洞察力。糖摄取在细胞的载体能力中起着至关重要的作用 蚊子和每年折磨着10多亿人的疾病的传播。因此，解开 喂蜜的神经基础将使新的基因靶标和控制它们的工具成为可能。