Contributions of Zebrafish to Our Understanding of the Function and Regulation of Sleep

Sleep is an essential behavioral state, but how and why animals sleep is poorly understood. These questions are being addressed using a variety of model systems, each with its own advantages and limitations. Here we review the contributions of zebrafish to our understanding of both mechanisms that regulate sleep and the functions of sleep. Initial zebrafish studies focused on defining sleep based on behavioral criteria and demonstrating that mechanisms that regulate mammalian sleep are conserved in zebrafish. More recent work, based on both specific hypothesis testing and large-scale screens, has provided novel insights into both mechanisms that regulate sleep and the functions of sleep. Studies using larval zebrafish showed that melatonin is essential for circadian regulation of sleep, and that both the serotonergic raphe and galanin play important roles in homeostatic regulation of sleep. These studies also identified the noradrenergic locus coeruleus as a hub that integrates wake- and sleep-promoting inputs to determine vigilance state. Work using zebrafish also revealed that repair of DNA damage is an important function of sleep, and provided support for the hypothesis that synaptic homeostasis is a function of sleep. Although the zebrafish was only recently developed as a sleep model and is used for this purpose by only a small number of labs, zebrafish studies have made important contributions to our understanding of both mechanisms that regulate sleep and functions of sleep. Based on recent advances in microscopy and genome editing technologies, studies using zebrafish are poised to provide important new insights into how and why animals sleep that would be difficult to achieve using other model systems.