Tytheridge, S. | bioRxiv Science

bioRxiv2025

Controlling malaria mosquito reproduction via the octopamine beta2 receptor

Mosquito reproduction in a broad sense involves multiple steps from acoustic recognition of mating partners to egg hatching. We show that the octopamine receptor AgOct{beta}2R controls different aspects of this process in a sexually dimorphic manner. AgOct{beta}2R knockout males present auditory defects that impair their ability to inseminate females, whilst knockout females are sterile. These phenotypes suggest AgOct{beta}2R as a target to impair mosquito reproduction at multiple levels. We test the reproductive effects of the insecticide amitraz, an AgOct{beta}2R agonist, showing that amitraz exposure reduces insemination in the lab but not in the field and has no effects on female sterility, excluding its applicability as a mating disruptor. Pharmacological assays reveal that AgOct{beta}2R sensitivity to amitraz is reduced compared to other arthropods, but its responses can be altered by modifying residues in the binding pocket. Together, our results establish AgOct{beta}2R as a promising target to disrupt mosquito reproduction but emphasize the necessity of developing new tools to exploit this approach.

neuroscience↗

bioRxiv2024

The GABAA receptor RDL modulates the auditory sensitivity of malaria mosquitoes.

Malaria mosquitoes mate in crowded, and noisy, swarms. A vital stage of their precopulatory behaviour involves detecting the faint flight tone of a mating partner amidst the noise from hundreds of other mosquitoes. This exquisite sensory performance is enabled by a complex auditory system with remarkable features. One such feature is their vast efferent control system, which provides the mosquito ear with the required plasticity to adapt to various external and internal changes. In this paper, we study the auditory role of GABA, one of the main efferent signalling molecules in the mosquito ear, and its interactions with octopamine, another neurotransmitter of the efferent network. We show that GABA is released in the malaria mosquito auditory nerve and that GABA receptors are expressed in the ear, including the GABAA receptor Resistance to Dieldrin (RDL), a target for the evolution of insecticide resistance. Using picrotoxin to antagonize RDL receptors, we discovered multiple auditory effects of GABA at the mechanical and electrical level. At the mechanical level, blocking RDL promotes the erection of antennal fibrillae and the cessation of flagellar self-sustained oscillations. These effects are not observed in knockouts of the octopamine receptor AgOct{beta}2, suggesting that RDL auditory mechanical effects are mediated through octopamine release in the mosquito ear. Electrically, picrotoxin injection increases the spontaneous firing of auditory neurons and direct current (DC) responses of the nerve to mechanical stimulation both in wildtype and AgOct{beta}2 mutants, indicating that RDL may also modulate auditory sensitivity via octopamine-independent pathways. In summary, our experiments uncover distinct auditory roles of GABA, as well as synergistic roles with octopamine. The data show a fundamental role of RDL in controlling the auditory function of malaria mosquitoes and implicate RDL signalling in mating of natural malaria mosquito populations.

neuroscience↗