Collaborative Research: Olfactory learning and neuromodulation in the Aedes aegypti mosquito

蚊子是疾病病原体的重要载体，每年在全世界造成100多万人死亡。我们知道蚊子通过它们灵敏的嗅觉来定位和叮咬人类。然而，并不是每个人都被蚊子叮咬，有些人被蚊子叮咬的次数比其他人多。是什么导致了蚊子叮咬偏好的差异？值得注意的是，蚊子可以根据过去的经验来学习和记忆，尤其是被动物或人拍打的经验。被拍打的经历可以改变它们的气味和叮咬偏好，但我们对蚊子大脑如何处理这些信息知之甚少。该项目将采用跨学科的方法，结合埃及伊蚊的新行为和电生理技术，了解气味学习是如何发生的，从而改变它们的叮咬行为。这些项目还将为本科生、研究生和博士后提供培训机会，目的是为他们独立从事科学事业做好准备。参加上进计划的高中生也将通过暑期研讨会和实验室体验参与该项目。在这个项目中，我们建立在我们最近的发现，多巴胺介导的学习和调节在蚊子的初级嗅觉系统，触角叶，是埃及伊蚊宿主偏好的关键。采用跨学科的方法，我们的合作团队将阐明多巴胺介导的可塑性在嗅觉回路中的作用。我们有三个目标：(1)我们将测试蚊子只学习特定气味的假设，对应于特定触角叶肾小球的调谐。(2)为了验证“可学习”的气味是由接受密集多巴胺神经支配的触角叶肾小球编码的。(3)验证多巴胺与气味同时输入导致蚊子触角叶项目神经元可塑性，使蚊子能够学习重要的嗅觉刺激的假设。我们认为，我们提出的实验可能为理解早期嗅觉回路中多巴胺能可塑性的贡献提供一个基本框架。此外，嗅觉行为，包括学习，对于蚊子的偏好和叮咬人类宿主至关重要，从而传播疾病，每年折磨近10亿人。因此，揭示蚊子学习的神经基础对于开发控制蚊子的新策略具有重要的潜力。该项目还将向学生介绍跨学科研究，并向高中生广泛传播昆虫神经生物学的重要性。参加上进计划的高中生将通过暑期研讨会和实验室体验参与该项目。最后，该项目还包括培养本科生、研究生和博士后，帮助他们为独立的科学事业做好准备。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Mosquitoes are important vectors of pathogens of disease, accounting for more than a million annual deaths worldwide. We know that mosquitos locate and bite humans by their sensitive sense of smell. However, mosquitoes do not bite everyone equally – some people are bitten more than others. What causes this difference in the mosquito’s biting preference? Remarkably, mosquitoes can learn and remember based on past experiences, particularly the experience of having an animal or person swat at them. The experience of being the target of a swat can modify their odor and biting preferences, but we know remarkably little about how this information is processed in the mosquito brain. This project will use an interdisciplinary approach that combines novel behavioral and electrophysiological techniques from Aedes aegypti mosquitoes to understand how odor learning takes place to modify their biting behaviors. These projects will also incorporate training opportunities for undergraduates, graduate students, and postdoctoral associates with the aim of preparing them for independent scientific careers. High School students in the Upward Bound Program will also participate in the project through summer seminars and lab experiences. In this project, we build on our recent findings that dopamine-mediated learning and modulation in the mosquito’s primary olfactory system, the antennal lobe, is critical for Aedes aegypti mosquito host preferences. Using an interdisciplinary approach, our collaborative team will elucidate the role of dopamine-mediated plasticity in olfactory circuits. We accomplish this with three Objectives: (1) We will test the hypothesis that mosquitoes only learn certain odors, corresponding to the tuning of specific antennal lobe glomeruli. (2) To test that “learnable” odors are encoded by antennal lobe glomeruli that receive dense dopaminergic innervation. And (3) to test the hypothesis that coincident dopamine and odor input cause plasticity of antennal lobe project neurons and allows mosquitoes to learn important olfactory stimuli. We suggest that our proposed experiments may provide a basic framework for understanding the contribution of dopaminergic plasticity in early olfactory circuits. Moreover, olfactory behaviors, including learning, are critical for mosquito preferences and biting of human hosts, and thereby spread diseases that afflict nearly a billion people annually. Therefore, unraveling the neural bases of learning in mosquitoes has important potential for developing new strategies for their control. The project will also introduce students to interdisciplinary research and broadly communicate insect neurobiology's importance to high school students. High School students in the Upward Bound Program will participate in the project through summer seminars and lab experiences. Finally, the project includes training undergraduates, graduate students, and postdoctoral associates and helps prepare them for independent scientific careers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.