title: Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants.
abstract: Sleep is a fundamental biological process conserved across the animal kingdom. The study of how sleep regulatory networks are conserved is needed to better understand sleep across evolution. We present a detailed description of a sleep state in adult zebrafish characterized by reversible periods of immobility, increased arousal threshold, and place preference. Rest deprivation using gentle electrical stimulation is followed by a sleep rebound, indicating homeostatic regulation. In contrast to mammals and similarly to birds, light suppresses sleep in zebrafish, with no evidence for a sleep rebound. We also identify a null mutation in the sole receptor for the wake-promoting neuropeptide hypocretin (orexin) in zebrafish. Fish lacking this receptor demonstrate short and fragmented sleep in the dark, in striking contrast to the excessive sleepiness and cataplexy of narcolepsy in mammals. Consistent with this observation, we find that the hypocretin receptor does not colocalize with known major wake-promoting monoaminergic and cholinergic cell groups in the zebrafish. Instead, it colocalizes with large populations of GABAergic neurons, including a subpopulation of Adra2a-positive GABAergic cells in the anterior hypothalamic area, neurons that could assume a sleep modulatory role. Our study validates the use of zebrafish for the study of sleep and indicates molecular diversity in sleep regulatory networks across vertebrates.
authors.affiliation: Howard Hughes Medical Institute, Stanford University, Palo Alto, California, USA.
authors.forename: Tohei
authors.initials: T
authors.lastname: Yokogawa
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Marin
authors.forename: Juliette
authors.initials: J
authors.lastname: Faraco
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pézeron
authors.forename: Lior
authors.initials: L
authors.lastname: Appelbaum
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rosa
authors.forename: Philippe
authors.initials: P
authors.lastname: Mourrain
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001143:Arousal / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008027:Light; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation; D007319:Sleep Initiation and Maintenance Disorders / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D029961:Zebrafish Proteins