A novel beta-adrenergic like octopamine receptor modulates the audition of malaria mosquitoes and serves as insecticide target

Abstract

Hearing is an essential sense in the life cycle of malaria mosquitoes. Within large swarms formed transiently at dusk, mosquitoes acoustically recognize their mating partners by their wingbeats. Indeed, malaria mosquitoes only respond to the flight tones of mating partners during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are still largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing. Among them, octopamine stands out as regulator of the auditory performance during swarm time. To explore octopamine roles in mosquito hearing, we carried out an in-depth analysis of octopamine-mediated effects on auditory function. We found that octopamine affects the properties of the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and it controls the erection of antennal fibrillae in males. We found that two different receptors are driving octopamine auditory roles, including a novel beta octopamine receptor. We also demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings identify octopamine signalling as a key component of hearing and mating partner detection in malaria mosquitoes, and as a potential novel target for mosquito control.

The auditory efferent system in mosquitoes

“…Lapshin and Vorontsov have reported functional specialization across scolopidia that differ in their frequency tuning Vorontsov, 2013, 2019). In Culex pipiens mosquitoes, eight groups of auditory neurons have been reported, a majority of them being sensitive to 190-270 Hz (Lapshin and Vorontsov, 2017), a frequency range that nicely encompasses the quadratic and cubic distortion product frequencies that are generated by the non-linear mixing of male and female flight tones and have been suggested to mediate the female detection by the male (Somers et al, 2022). Whether scolopidia in the mosquito JO are tonotopically arranged is still unknown.…”

“…A recent paper has reported the expression of a broad range of receptors from different neurotransmitter families in the ear of male An. gambiae mosquitoes (Georgiades et al, 2022), including not only octopamine, serotonin and GABA, but also other classical neurotransmitters such as acetylcholine (ACh) and glutamate. It is therefore plausible that ACh and glutamate are also released from efferent terminals in the mosquito JO.…”

“…Interestingly, the same study also found expression of multiple neurotransmitter receptors in the JO of female An. gambiae mosquitoes (Georgiades et al, 2022), despite scarce labelling with presynaptic markers (Su et al, 2018). Due to the smaller size of the female JO compared to the male, it is plausible that volume transmission mechanisms suffice to mediate the diffusion of neurotransmitters from the brain to the receptors in the JO (Liu et al, 2021;Guidolin et al, 2022).…”

“…Furthermore, it is also possible that some of the neurotransmitter Frontiers in Cell and Developmental Biology frontiersin.org receptors localize to the auditory nerve connecting the JO to the brain. Dissections for RNA-Seq involve removing whole pedicel from the head, making it is plausible that the dissected material might contain non-JO axonal sections (Georgiades et al, 2022), potentially explaining the discrepancy between transcriptomic and immunohistochemistry data.…”

“…Sensory efferent systems are therefore descending pathways from the central nervous system to sensory organs that modulate their function (Ryugo et al, 2010). The mosquito auditory efferent system in mosquitoes, which contains a variety of neurotransmitters, multiple distinct sites of release and different functional effects, matches the complexity of their vertebrate counterparts (Andrés et al, 2016;Su et al, 2018;Georgiades et al, 2022).…”