Melatonin promotes sleep by suppressing responses to visual stimuli via MT1 receptors

Sleep is regulated by a homeostatic process that increases sleep propensity with time spent awake and a circadian process that determines when most sleep occurs during the 24-h circadian cycle. While several factors mediate homeostatic regulation of sleep in a partially redundant manner, circadian regulation of sleep is abolished in zebrafish that lack melatonin, indicating that melatonin is indispensable for circadian regulation of sleep in this diurnal species. However, the mechanisms through which melatonin promotes sleep are unclear. Here, we show that melatonin is both necessary and sufficient for sleep in zebrafish due to signaling via melatonin receptor 1a paralogs. We found that these receptors are highly expressed in neurons that receive and process visual information and that melatonin suppresses behavioral responses to visual stimuli. These results indicate that circadian regulation of sleep is implemented, at least in part, by the suppression of responses to environmental stimuli, which is an essential feature of sleep.