A gut-secreted peptide controls arousability through modulation of dopaminergic neurons in the brain

Since sensory information is always present in the environment, animals need to internally regulate their responsiveness to fit the context. During sleep, the threshold for sensory arousal is increased so that only stimuli of sufficient magnitude can cross it. The mechanisms that make arousability flexible are largely mysterious, but they must integrate sensory information with information about physiology. We discovered a gut-to-brain signaling pathway that uses information about ingested nutrients to control arousability from sleep, without affecting sleep duration. Protein ingestion causes endocrine cells in the Drosophila gut to increase production of CCHa1, a peptide that decreases sensory responsiveness. CCHa1 is received by a small group of brain dopaminergic neurons whose activity gates behavioral responsiveness to mechanical stimulation. These dopaminergic neurons innervate the mushroom body, a brain structure involved in determining sleep duration. This work describes how the gut tunes arousability according to nutrient availability, allowing deeper sleep when dietary proteins are abundant. It also suggests that behavioral flexibility is increased through independent tuning of sleep depth and duration.