CHAPTER 11 Monitoring Sleep and Arousal in Zebrafish Jason Rihel * , David A. Prober † , and Alexander F. Schier *,‡,§,{ * Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts † Division of Biology, California Institute of Technology, Pasadena, California ‡ Division of Sleep Medicine, Harvard University, Cambridge, Massachusetts § Center for Brain Science, Harvard University, Cambridge, Massachusetts { Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts I. Introduction II. Behavior, Genetics, and Pharmacology of Zebrafish Sleep A. Behavior B. Genetics and Pharmacology III. Methods for Monitoring Sleep/Wake Behavior in Zebrafish A. Methodological Considerations—from Drosophila to Danio B. Experimental Design and Setup C. Monitoring and Analysis of Sleep/Wake Behaviors IV. Conclusion References Abstract Zebrafish has emerged in the past 5 years as a model for the study of sleep and wake behaviors. Experimental evidence has shown that periods of behavioral quiescence in zebrafish larvae and adults are sleep-like states, as these rest bouts are regulated by the circadian cycle, are associated with decreases in arousal, and are increased following rest deprivation. Furthermore, zebrafish share with mammals a hypocretin/orexin system that promotes wakefulness, and drugs that alter mammalian sleep have similar effects on zebrafish rest. In this chapter, we review the zebrafish sleep literature and describe a long-term, high-throughput monitoring system for observing sleep and wake behaviors in larval zebrafish. METHODS IN CELL BIOLOGY, VOL. 100 978-0-12-384892-5 Copyright Ó 2010 Elsevier Inc. All rights reserved. 281 DOI: 10.1016/B978-0-12-384892-5.00011-6