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

蚊子是疾病病原体的重要媒介，全世界每年有100多万人死于蚊子。我们知道蚊子通过其敏感的嗅觉来定位和叮咬人类。然而，蚊子对每个人的叮咬并不是一样的--有些人比其他人被叮得更多。是什么导致了蚊子叮咬偏好的这种差异？值得注意的是，蚊子可以根据过去的经历学习和记忆，特别是被动物或人殴打的经历。成为蚊子目标的经历可以改变它们的气味和咬人偏好，但我们对这些信息在蚊子大脑中是如何处理的知之甚少。这个项目将使用一种跨学科的方法，结合埃及伊蚊的新的行为和电生理技术来了解气味学习是如何发生的，以改变它们的叮咬行为。这些项目还将包括对本科生、研究生和博士后助理的培训机会，目的是让他们为独立的科学生涯做好准备。参加向上跳跃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，我们基于我们最近的发现，即多巴胺介导的学习和蚊子主要嗅觉系统--触角叶的调制，对埃及伊蚊宿主的偏好至关重要。利用跨学科的方法，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。我们通过三个目标来实现这一点：(1)我们将检验这样一个假设，即蚊子只学习某些气味，对应于特定触角叶小球的调节。(2)测试“可学习”气味是由接受密集多巴胺能神经支配的触角叶小球编码的。以及(3)检验这样一种假设，即多巴胺和气味的同时输入会导致触角叶投射神经元的可塑性，并允许蚊子学习重要的嗅觉刺激。我们认为，我们提出的实验可能为理解多巴胺能可塑性在早期嗅觉回路中的作用提供了一个基本框架。此外，包括学习在内的嗅觉行为对蚊子的偏好和人类宿主的叮咬至关重要，从而传播每年困扰近10亿人的疾病。因此，解开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。参加向上跳跃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，该项目包括培训本科生、研究生和博士后助理，帮助他们为独立的科学生涯做好准备。该奖项反映了NSF的法定使命，并通过使用基金会的学术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.