How does zebrafish sleeep?

Zebrafish is one of the most important model organisms in biomedical research, and there is an interesting paper on PLoS Biology studying the sleep of zebrafish.

Yokogawa T. et al. used adult fish sleep recording system (AFSRS), a device videotracking fish illuminated by an infrared source under light and dark conditions, to conduct the behavioral studies. They confirmed that, as in humans, zebrafish sleeps, with the characteristics of reversible periods of immobility, increased arousal threshold, and place preference. Similar to the homeostatic regulation in mammals, rest deprivation, by electrical stimulation, is followed by a sleep rebound, but mostly in the dark. However, rest deprivation by the light does not get obvious sleep rebound afterwards. In fact, light supresses sleep in zebrafish, which is very different from human and mammals, but close to birds.

On the molecular aspect, the authors studied hypocretin receptor and hypocretin, the only neurochemical system known to be involved in narcolepsy, a clear human sleep disorder. Using in situ hybridization, they showed that hypocretin receptor (hcrtr) is widely expressed in the brain of zebrafish embryos and adults. However, histologically, her hypocretin receptor does not colocalize with major monoaminergic cell groups in zebrafish embryos and adults. Neither does it colocalized with cholinergic cell groups. In contrast, it colocalizes with large populations of GABAergic neurons, including a subpopulation of Adra2a-positive GABAergic cells in the anterior hypothalamic area, where nervous system meets endocrine system.

Then they went zebrafish with mutation of hypocretin receptor. These fish lacks hypocretin receptor, and behaves disparately: sleep amounts were decreased by 20% - 30% during the night, 60%-70% increase in the number of sleep-wake transitions, 60% decrease in sleep bout length during the night. In short, hcrtr null mutant fish has short and fragmented sleep.

The authors further employed pharmalogical approaches by intracerebralventricular injection of hypocretin. Injection of hypocretin-2 was inactive due to rapid metabolism. On the other hand, injection of hypocretin-1 begets reduction in locomotor activity, which is dose-dependent. This effect in wild type zebrafish, as imagined, is abolished in hcrtr null mutant.

It seems the endpoint presentation of zebrafish lacking hypocretin receptor is contrary to narcolepsy in human. The pharmalogical outcome of hypocretin is right opposite to that in mammals, which promotes wakeness and increases locomotion. In regard to neuroanatomy, hypocretin receptor in zebrafish colocalizes with inhibitory neurons, rather than stimulating cell groups in mammals. I would like to quote the authors' words, this indicates "molecular diversity in sleep regulatory networks across vertebrates".

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Tags: zebrafish, model organism, developmental biology, sleep disorder, insomnia, narcolepsy, neurology, behavior biology, molecular biology, hypocretin, narcolepsy, orexin, hypocretin receptor, histology, hcrtr, hypocretin-1, hypocretin-2, HCRTR, pharmacology, hypothalamus, monoamine, monoaminergic, catecholamine, cholinergic, GABA, GABAergic, intracerebralventricular, evolution, conserved, diversity, phylogenesis, Medicine, Medicine-Molecular Biology, Medicine-Developmental Biology, Medicine-Behavior Biology, Medicine-Pharmacology, Medicine-Histology, Biomedical Science, Medical Science