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Chronic sleep disturbance is a problem for a significant number of Americans, but the mechanisms that control sleep and wakefulness are largely unknown. The Schier lab is using zebrafish to investigate the genes and circuits that regulate sleeping. Zebrafish are a useful model system because both genetic and imaging approaches can be easily combined to study complex behaviors in a vertebrate system. Importantly, zebrafish have behaviors that distinguish awake fish from sleeping fish (sleeping fish move less and require stronger stimuli than awake fish to initiate movement), and have similar brain chemistry to humans, expressing peptides that have been implicated in human sleep disorders. As a result, Dr. Schier has developed zebrafish as a model system for studying sleep and screening sleep-altering drugs. The lab is using genetic and pharmacological screens to isolate sleep regulators and electrophysiological and imaging approaches to dissect sleep circuits.

Zebrafish has been developed as a model for drug characterization. As zebrafish have similar brain chemistry to humans, especially the neurochemistry underlying their rest/wake cycles, they can be used to screen compounds affecting behavior. In addition, using zebrafish instead of mice for drug profiling greatly reduces animal costs. The Schier lab has developed an automated screening technique for monitoring sleep/rest cycles in zebrafish, allowing the study of the effects of drug candidates on behavior. The effects of novel drugs can be compared to known drugs and side effects can be deduced from behavioral profiling.

The genetic tractability of zebrafish also allows them to be used for genetic screens. Dr. Schier has developed a model of insomnia in zebrafish that is based on hypocretin (Hcrt) overexpression. Hcrt is a known mammalian sleep/wake regulator, and the Schier lab has found that the expression pattern and activity of larval zebrafish Hcrtis similar to those in mammals. As a result, Hcrt overexpression affects zebrafish waking cycles, promoting wakefulness and inhibiting rest. This zebrafish insomnia model can be used for the investigation of drugs to combat insomnia.