The representation of human odor in the mosquito brain

Summary Mosquitoes transmit pathogens that are a major worldwide health problem. Over 500,000 deaths are caused by mosquito-borne diseases annually. Aedes aegypti mosquitoes are arboviral vectors that transmit the pathogens that cause Dengue, Zika, and other illnesses. Only female mosquitoes bite, and they do so to obtain the nutrients required to reproduce. To find humans to bite, female mosquitoes must integrate multiple sensory cues. To find humans, they rely heavily on human body odor, which is composed of hundreds of chemicals, and carbon dioxide emitted in breath. The study of the mechanisms that mosquitoes use to detect odorant chemicals and carbon dioxide have been focused on the peripheral sensory neurons that detect odorants and other sensory cues. It is essential to move beyond the sensory periphery and study the central nervous system because mosquitoes use redundant sensory cues to detect humans: mutant mosquitoes lacking key receptors can still find humans, highlighting this system's robustness and the importance of studying it holistically in order to disrupt biting. Almost nothing is known about the neurons that are downstream of the olfactory sensory neurons in Ae. aegypti, including how sensory cues converge, and what circuit mechanisms make the mosquito olfactory system so resistant to perturbation. The olfactory system of Ae. aegypti mosquitoes provides a rare opportunity to study fundamental questions about olfaction while also solving an urgent biomedical question. The goal of this work is threefold: 1), to identify which neurons encode human odor in the mosquito brain, 2) determine how olfactory information converges to guide human host seeking, and 3) identify circuit mechanisms that combine information about odor and carbon dioxide. To achieve these goals, we will develop new techniques to study the mosquito central nervous system. Trans-synaptic labelling is a fundamental approach used in neuroscience research because it can identify synaptically connected neurons, thereby enabling the study of interconnected neurons in a circuit or pathway. Currently, there are no methods for trans-synaptic labelling in non-model insects, including Ae. aegypti. We will develop a method for trans-synaptic labelling in Ae. aegypti based on the trans-tango system used in Drosophila melanogaster. Using this approach, we will generate transgenic mosquito strains to examine the anatomy, activity, and the transcriptional profile of targeted neurons. We will use these essential neuroscience methods to study the central circuits that detect human odor and ultimately drive host seeking behavior. This will lay the groundwork to develop new strategies to intervene in mosquito biting and also add to our fundamental understanding of the circuits that underly olfactory-driven behaviors.