Biogenic amines in malaria mosquitoes: from hearing to swarming behaviour

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.

The rapid emergence of insecticide resistance among mosquito populations, alongside behavioural adaptations enabling evasion of control tools, makes a compelling case for developing novel control interventions. Due to their necessity for mating, hearing and swarming are promising targets. However, they have been underexploited due to extensive gaps in knowledge of the mosquito auditory behaviour and the molecular mechanisms involved. This project will produce data in two main areas with potential public health impact: i) physiological and behavioural data of mosquito auditory sensitivity that can be translated into the development of acoustic traps to lure and kill mosquitoes and inform the development of acoustic sensors as a novel high-throughput method for mosquito surveillance; ii) potential of interfering BA signalling to impair mosquito mating. OA/5-HT signal through G-protein coupled receptors that are considered promising targets for the development of next generation insecticides. Interestingly, OA (invertebrate counterpart of noradrenaline) is preferably synthetized in invertebrates and is only present as traces in mammals, so their receptors are promising potential targets for highly specific insecticides. Building on this project, I will develop a research career focused on providing rigorous physiological and behavioural data to incorporate acoustic traps and swarming impairment approaches into the spectrum of interventions to fight mosquito vector diseases.
The findings will be relevant for a broad audience. Medical entomologist and other public health stakeholders working in malaria control will be interested in the results, as evidence-based practices for malaria control con be derived from them. To reach them I will attend applied research conferences where different actors working on malaria control come together.
The project will also shed light on the molecular mechanisms underlying a fascinating sensory organ. I will characterize the first auditory efferent system describe in insects. This is highly relevant for other academic audiences, such as insect physiologists and vector biologists. Findings will reach these scientists by participating in conferences and publishing the research in high impact and open access journals.
The general public will also benefit from the results, as mosquito-borne diseases are a cause of mortality and morbidity worldwide, and mosquito species with the potential to transmit disease are spreading in Europe, due to the increase in international travel and the climate change. Different outreach activities will be organized to ensure that the research relevance has an impact on the wider public. In particular, public engagement activities will be performed in schools, both in UK and Tanzania, to ensure that future generations understand the importance of mosquito-borne disease and how to better protect themselves against mosquito bites.