Olfactory receptors and neurons regulating odor-guided behaviors in mosquitoes

调节蚊子气味引导行为的嗅觉受体和神经元

• 批准号: 9982760
• 负责人: Christopher John Potter
• 金额: $ 52.84万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-17 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982760
• 关键词: Address; Adoption; Aedes; Affect; Agriculture; Anatomy; Anopheles Genus; Anopheles gambiae; Arthropod Vectors; Behavior; Behavioral Assay; Biological Assay; Biology; Bite; Calcium; Cessation of life; Chemicals; Chironomus thummi; Cues; Culex (Genus); Culicidae; Data; Developed Countries; Development; Disease; Disease Vectors; Electrophysiology (science); Eugenol; Exhibits; Fleas; Genetic; Genetic Techniques; Hair; Human; Human body; Image; Insect Repellents; Insect Vectors; Insecta; Lead; Link; Malaria; Masks; Maxilla; Measures; Methodology; Methods; Mites; Molecular Target; Neurobiology; Neurons; Odorant Receptors; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Pain; Parasites; Pattern; Plasmodium; Production; Reagent; Research; Sensory; Signal Transduction; Smell Perception; System; Testing; Ticks; Time; Vector-transmitted infectious disease; Work; base; cost; design; genetic approach; improved; insight; neural circuit; neurogenetics; novel; olfactory sensory neurons; prevent; response; side effect; skin irritation; transcriptome sequencing; vector control

Project Abstract/Summary Anopheles gambiae mosquitoes, as the insect vector for the Plasmodium parasite that causes malaria, were responsible for the deaths of >450,000 people last year. Fortunately, mosquitoes have a weakness that our research aims to exploit. Mosquitoes use their sense of smell for most human host-seeking behaviors. This suggests that targeting a mosquito's sense of smell could lead to effective measures that prevent bites and the spread of diseases. Indeed, spatial repellents are volatile odorants that effectively disrupt host-seeking behaviors and keep mosquitoes from approaching. They have widespread use in developed nations as personal protective measures, but global adoption is limited due to high costs, unwanted side-effects (such as skin irritation), or the need to use high-concentrations to remain effective. A major limitation to the identification of new, more tractable, repellents is a lack of understanding of how spatial repellents promote repulsion by impacting the mosquito's sense of smell. This is primarily due to challenging technical hurdles needed to link repellent and other odorants to a variety of olfactory neuron functions. Our introduction of the QF2/QUAS genetic binary system into Anopheles mosquitoes overcomes previous technical barriers, and now enables us to directly visualize the response of olfactory neurons, in living mosquitoes, to repellents and human body odors. Using a combination of calcium imaging, single sensillum electrophysiological recordings, and RNA-seq along with our established and novel genetic techniques, we will test the hypothesis that (1) spatial mosquito repellents function by masking, activating, or scrambling the activity of olfactory neurons. We will examine the activity patterns of olfactory neurons in living Anopheles gambiae mosquitoes when stimulated by 20 commonly used mosquito repellents in the presence and absence of human odorants. In addition, we will identify the odorant receptors expressed by olfactory neurons exhibiting altered activity patterns in response to each repellent. Using a combination of genetic approaches (aimed at modulating the function of targeted olfactory neurons) and behavioral assays, we will test the hypothesis that (2) spatial repellents promote repellent behaviors by altering olfactory system signaling. We will experimentally determine which olfactory neurons and what types of olfactory neuron activity changes are either necessary and/or sufficient to drive repellent behaviors. The proposed studies are significant because we will gain new mechanistic insights into how mosquito repellents target the mosquito's sense of smell and enable the development of rationale biology-based strategies to identify new repellents that are cheaper, safer, and more effective for use on a global scale to prevent the spread of disease.

项目摘要/总结 冈比亚按蚊是引起疟疾的疟原虫寄生虫的昆虫媒介， 去年造成超过 45 万人死亡。幸运的是，蚊子也有弱点 我们的研究旨在利用这一点。大多数人类蚊子利用嗅觉寻找宿主 行为。这表明针对蚊子的嗅觉可能会导致采取有效措施 防止叮咬和疾病传播。事实上，空间驱虫剂是挥发性气味剂，可以有效地驱除 扰乱寻找宿主的行为并阻止蚊子接近。它们广泛用于 发达国家作为个人防护措施，但由于成本高昂，全球采用受到限制， 不需要的副作用（例如皮肤刺激），或需要使用高浓度来保持 有效的。识别新的、更容易处理的驱虫剂的一个主要限制是缺乏 了解空间驱虫剂如何通过影响蚊子的嗅觉来促进排斥。 这主要是由于将驱虫剂和其他气味剂与气味联系起来需要具有挑战性的技术障碍。 多种嗅觉神经元功能。我们将QF2/QUAS遗传二元系统引入 按蚊克服了以前的技术障碍，现在使我们能够直接可视化 活蚊子的嗅觉神经元对驱虫剂和人体气味的反应。使用 结合钙成像、单感器电生理记录和 RNA-seq 利用我们已建立的新颖的遗传技术，我们将检验以下假设：（1）空间蚊子 驱虫剂通过掩盖、激活或扰乱嗅觉神经元的活动来发挥作用。我们将 检查活体冈比亚按蚊嗅觉神经元的活动模式 在有或没有人类气味的情况下，由 20 种常用驱蚊剂刺激。 此外，我们将鉴定嗅觉神经元表达的气味受体，这些受体表现出改变 对每种驱虫剂的反应的活动模式。使用遗传方法的组合（旨在 调节目标嗅觉神经元的功能）和行为测定，我们将测试 假设 (2) 空间驱避剂通过改变嗅觉系统促进驱避行为 发信号。我们将通过实验确定哪些嗅觉神经元以及哪些类型的嗅觉 神经元活动的变化对于驱动排斥行为是必要的和/或充分的。这 拟议的研究意义重大，因为我们将获得关于蚊子如何 驱虫剂针对蚊子的嗅觉，并促进基于生物学原理的开发 确定在全球范围内使用更便宜、更安全、更有效的新驱虫剂的策略 以防止疾病传播。