# Morphological specializations of mosquito CO2-sensing olfactory receptor neurons

## TL;DR

This paper reveals unique structural features in mosquito CO2-sensing neurons that may enhance their ability to detect human hosts.

## Contribution

The study provides the first detailed 3D anatomical characterization of CO2-sensing neurons in Aedes aegypti mosquitoes.

## Key findings

- CO2-sensing cpA neurons have an 8-12 times larger dendritic surface area compared to neighboring neurons.
- cpA neurons exhibit a unique axonal structure with mitochondria-rich varicosities and are ensheathed by glial and auxiliary cells.
- The cpA dendrites are folded into lamellae, increasing CO2 exposure and potentially improving detection efficiency.

## Abstract

Carbon dioxide (CO2) emitted by human hosts is a critical cue that mosquitoes use for host detection, yet the nanoscale three-dimensional (3D) structure of their CO2-sensing neurons and associated cells remains unclear. Elucidating the anatomy of these cells will yield structural insight into the sensory biology which drives mosquito−host interactions. Using volume electron microscopy, we reveal that Aedes aegypti CO2-sensing neurons exhibit striking structural specializations—including enlarged CO2-sensing surface areas, unique axonal architecture enriched with mitochondria, and unusual somatic ensheathing by support and glial cells—that likely enhance CO2 detection and support signal transmission. Our detailed anatomical characterization provides a structural basis for the mosquito’s exceptional host-seeking capabilities.

Hematophagous mosquitoes use CO2 as a key arousal signal that gates behavioral responses to host-derived cues. In Aedes aegypti, CO2 is detected by olfactory receptor neurons (ORNs) housed in the sensory hairs (sensilla) on the maxillary palp. While the molecular mechanism and behavioral significance of CO2 sensing have been well studied in mosquitoes, the nanoscale three-dimensional structures of their CO2-sensing ORNs and associated cells have remained unclear. Using serial block-face scanning electron microscopy, we characterize the CO2-sensing cpA neuron and its odor-sensitive neighbors, cpB and cpC, within the capitate sensilla of A. aegypti. Notably, cpA neurons are significantly larger, with an outer dendritic surface area 8 to 12 times greater than that of cpB and cpC neurons. This expanded CO2-sensing surface arises from its unique architecture, consisting of numerous flattened dendritic sheets folded into intricate lamellae. In contrast, cpB and cpC dendrites exhibit sparse, narrow cylindrical branches. Moreover, the cpA axon displays a prominent pearls-on-a-string morphology, with numerous mitochondria-rich, nonsynaptic varicosities connected by thin cables. Remarkably, a glial cell and an auxiliary cell together ensheathe the cpA soma but not cpB or cpC, suggesting a specialized role in supporting cpA function. Compared to Drosophila CO2-sensitive ORNs, a larger portion of the cpA outer dendrite is embedded within the sensillum cuticle, potentially improving access to environmental CO2. These findings reveal key morphological specializations of cpA neurons, thereby advancing our understanding of mosquito sensory biology and laying the groundwork for future studies on the molecular basis and functional ramifications of these anatomical adaptations.