What are the molecular and cellular mechanisms that link neurological disorders and sleep disturbances? The transparent zebrafish model could bridge this gap in knowledge due to its unique genetic and imaging toolbox, and amenability to high-throughput screening. Sleep is well-characterized in zebrafish and key regulators of the sleep/wake cycle are conserved, including melatonin and hypocretin/orexin (Hcrt), whereas novel sleep regulating proteins are continually being identified, such as Kcnh4a, Neuromedin U, and QRFP. Sleep deficiencies have been observed in various zebrafish models for genetic neuropsychiatric disorders, ranging from psychomotor retardation and autism to anxiety disorders. Understanding the link between neuropsychiatric disorders and sleep phenotypes in zebrafish may ultimately provide a platform for identifying therapeutic targets for clinical trials in humans.
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