Post-biting behavioral reprogramming underlies reproductive efficiency in Aedes aegypti mosquitoes

The global spread and increasing populations of disease vector mosquitoes expose hundreds of millions of people to mosquito-borne illnesses each year. Female Aedes aegypti mosquitoes, global vectors of dengue, require protein from host blood to support egg development and undergo repeated cycles of blood-feeding and egg-laying. After biting, females temporarily alter their behavioral state and suppress host-seeking while using blood-derived nutrients to develop eggs. Host-seeking suppression ends once eggs are laid. While this period has generally been thought of as one of behavioral inactivity, we reveal that it instead reflects behavioral reprogramming, during which females transition from post-blood-meal inactivity into active searching for egglaying sites. Females with mature eggs show a distinct behavioral state characterized by increased locomotor activity and a shift in circadian behavioral timing, leading to nocturnal humidity-seeking and egg-laying in an otherwise diurnal species. We show that the circadian clock gene cycle is critical for regulating this transition; its absence disrupts the timing of oviposition behaviors, leading to poor site selection and reduced predicted offspring survival. These findings suggest that during egg development, circadian clock-dependent behavioral reprogramming triggers nocturnal hyperactivity and oviposition site search, an essential process for mosquito reproduction and population viability.