Biogenic amines in malaria mosquitoes: from hearing to swarming behaviour

蚊子比其他节肢动物对声音更敏感，这得益于它们迷人的微小触角耳朵——约翰斯顿器官（JO）。在一个只有针尖那么小的器官里，雄性蚊子拥有大约15000个听觉神经元，大致相当于人类耳蜗的毛发数量。蚊子用它们复杂的JO来识别交配伴侣的飞行音调。每天日落时分，雄蚊聚集成一群，吸引雌蚊。在蜂群中，雄性和雌性通过拍打翅膀来探测对方。由于蚊子交配的必要性，交配前的声音相互作用和群体行为是蚊虫控制工具的主要目标。尽管如此，蚊子群集行为的神经生物学和诱导它的生理机制几乎完全未知。我们最近展示了蚊子的JO功能是如何被听觉传出系统调节的。这是值得注意的，因为人们认为听觉传出控制只存在于脊椎动物中。我们发现生物胺章鱼胺和血清素在蚊子JO中释放，并调节声音引起的机械和电反应，可能有助于JO作为声音探测器的复杂性。有趣的是，生物胺可以诱导其他昆虫的群体和社会行为。综上所述，考虑到蚊子的听觉和群体行为之间的密切关系，我假设它们也会诱导蚊子聚集在群体中，并调整蚊子对交配伴侣飞行音调的听觉敏感性，以最大限度地提高交配成功率。我认为干扰5 -羟色胺和章鱼胺信号通路可能是一种新的蚊子控制目标，可以损害听力和蜂群，从而阻碍蚊子交配。我的初步数据支持这一假设：i)蚊子聚集时，蚊子JO中章鱼胺和血清素受体的水平会发生变化，ii)雄蚊在聚集时JO的听觉敏感性会增加，注射章鱼胺后也会产生这种效果。在这个项目中，我将采用多学科方法，结合分子生物学、生理学和行为学领域，研究章鱼胺和血清素在传播疟疾的冈比亚按蚊中引起的生理和行为变化，并宣布设计新的媒介控制工具。为了研究这一点，我将首先分析蚊子JO中八胺能和血清素能信号与生物钟之间的联系。我将研究章鱼胺和血清素水平是否在群集期间发生变化，以及这些变化如何反映听觉敏感性的变化。然后，我将通过产生血清素和章鱼胺受体突变体来破坏这些途径，并研究听觉和群体行为表型。最后，我的目标是将这些发现转化为创新的蚊虫控制工具，利用所获得的知识在疟疾流行国家的半野外环境中破坏群体行为。

Mosquitoes are more sensitive to sound than any other arthropod, by means of their fascinating tiny antennal ears, the Johnston 's organ (JO). In an organ smaller that a pin's head, male mosquitoes harbour around 15,000 auditory neurons roughly equalling the number of hair in human cochlea. Mosquitoes use their sophisticated JO's to recognize the flight tones of mating partners. Every day around sunset, male mosquitoes aggregate in areal swarms that attract females. Within swarms, male and female acoustically detect each other by their wing beats. Due to the necessity for mosquito mating, pre-mating acoustic interactions and swarming behaviour are prime targets for mosquito control tools. Despite this, the neurobiology of mosquito swarming behaviour, and the physiological mechanisms that induce it, are almost entirely unknown.We have recently shown how the mosquito JO function is modulated by an auditory efferent system. This is remarkable as auditory efferent control was believed to exist only in vertebrates. We show that the biogenic amines octopamine and serotonin are released in the mosquito JO and modulate sound-induced mechanical and electrical responses, likely contributing to JO's sophistication as sound detector. Interestingly, biogenic amines induce swarming and social behaviour in other insects. Taken together and given the intimate relationship between hearing and swarming behaviour in mosquitoes I hypothesized that they also induce mosquito aggregation in swarms and tune the mosquito auditory sensitivity to the flight tone of mating partners to maximize mating success. I argue that interfering with serotonin and octopamine signalling pathways could be a novel mosquito control target to impair hearing and swarming and consequently hinder mosquito mating. My preliminary data support this hypothesis: i) the levels of octopamine and serotonin receptors in the mosquito JO change during the time when mosquitoes are swarming, ii) the auditory sensitivity of male mosquito JO increases during swarming, and this effect is mimicked after injecting octopamine. In this project, I will use a multidisciplinary approach bridging the fields of molecular biology, physiology and behaviour to study the physiological and behavioural changes induced by octopamine and serotonin in malaria-transmitting Anopheles gambiae mosquitoes with the declared goal of devising novel vector control tools. To investigate this, I will first analyse the connection between the octopaminergic and serotonergic signalling in the mosquito JO and the circadian clock. I will study if octopamine and serotonin levels change during swarming and how these changes reflect shifts in auditory sensitivity. I will then disrupt these pathways by generating serotonin and octopamine receptor mutants and study the auditory and swarming behaviour phenotypes. Finally, I aim to translate these findings into innovative mosquito control tools by using the acquired knowledge to disrupt swarming behaviour in semi-field settings in a malaria endemic country.