Molecular basis of chemosensing by internal sensory neurons in Drosophila larvae

Interoceptive neurons monitor the chemical and physical state of the body, providing critical information to the central nervous system that maintains homeostasis and promotes survival. The circuit and molecular basis for these interoceptive senses remain under active investigation. A population of larval Drosophila sensory neurons, the tracheal dendrite (td) neurons, extend dendrites along respiratory organs and provide a tractable model for investigating the cellular and molecular basis of internal chemosensation. Here, we show that partially overlapping populations of td neurons respond to decreases in O2 and increases in CO2. To define the molecular basis of these responses, we examined the roles of atypical soluble guanylyl cyclases (Gycs) and gustatory receptors (Grs). We found that Gyc88E/Gyc89Db were required for hypoxia-evoked activity, whereas Gr28b was required for responses to CO2. Targeted expression of Gr28b.c isoform in td neurons restored responses to CO2 in mutant larvae and conferred ectopic sensitivity to CO2 within the td network. We further found that gas-sensitive td neurons were activated upon prolonged larval burrowing, a natural-like feeding-associated behavior. Together, these findings reveal molecular mechanisms that enable interoceptive neurons to monitor respiratory gases and advance a Drosophila model for studying the neural and molecular basis of internal chemosensation.