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Sleep and circadian rhythms are a part of everyone's daily life, yet many of us never take the time to appreciate the underlying genetic and molecular mechanisms that control these profound changes in physiological state. Clearly, sleep and circadian rhythms exert their influence at multiple physiological levels from gene expression to intracellular signaling cascades to integrated systemic responses. Recently, exciting new discoveries have advanced our understanding of the genetic basis of sleep and circadian rhythms. This issue of the Journal of Applied Physiology introduces a three-month Highlighted Topics series exploring the functional genomics of sleep and circadian rhythms.

The mini-reviews invited for this series provide a balance between the two focal points of this topic, namely sleep and circadian biology. In each of the next three issues, the Journal will feature one mini-review in the area of sleep and another in the area of circadian biology. A mini-review in the current issue entitled "How sleep deprivation affects gene expression in the brain: a review of recent findings" by Dr. Chiari Cirelli explores the long-asked question regarding the biological purpose of sleep. Dr. Cirelli presents her findings describing the systematic screening of brain gene expression in rats that have all undergone various forms and durations of sleep deprivation. Her results show that the transition from sleep to wakefulness can affect basic cellular functions, such as RNA and protein synthesis and neuroplasticity. Additionally, long periods of sleep deprivation provide unique changes of gene expression in the cortex. Accompanying Dr. Cirelli's mini-review in this month's issue is a contribution from Drs. Erik Herzog and William Schwartz entitled "A neural clockwork for encoding circadian time." In this mini-review, Drs. Herzog and Schwartz examine how intracellular regulatory molecules function in the oscillatory mechanism of the circadian clock. They provide evidence that the circadian clock is a self-sustaining oscillator with a period of ~24 h. This circadian clock controls a wide variety of physiological and behavioral systems and has its master pacemaker located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. These authors also explore how individual SCN cells interact to create an integrated tissue pacemaker with coherent metabolic, electrical, and secretory rhythms. Furthermore, they discuss how such circadian clock outputs are converted into temporal programs for the whole organism. They emphasize that the circadian timekeeping system presents a unique and powerful model for investigating the cellular and molecular mechanisms that underlie behavioral-state control at multiple levels of biological organization from intracellular molecules and gene expression to integrated patterns of physiology and performance.

The first mini-review in the February issue, entitled "Molecular genetic studies on sleep-wake regulation," by Dr. Osamu Hayaishi, explores molecular genetic approaches for researching the mechanisms of sleep-wake regulation with a special emphasis on the prostaglandin D₂ system. Dr. Hayaishi focuses on recent experimental evidence, primarily in knockout and transgenic mice, indicating a role of the prostaglandin D₂ system in the molecular genetics of sleep and wakefulness. The molecular genetic approach also distinguishes those mechanisms involved in the regulation of rapid eye movement vs. non-rapid eye movement sleep states. The second mini-review in the February issue, entitled "Human sleep-wake regulation and circadian rhythmicity," by Drs. Derk-Jan Dijk and Steven Lockley, focuses on human research. These authors emphasize that the human sleep-wake cycle is not simply driven by the circadian pacemaker in the SCN but is generated through complex interactions among circadian rhythmicity, a sleep-wake oscillatory process, circadian photoreception, as well as feedback from the sleep-wake cycle into these processes. Their review synthesizes recent developments related to circadian sleep propensity rhythm, sleep homeostasis, and circadian photoreception.

In the March issue, a mini-review entitled "Genetic dissection of sleep" by Drs. Medhi Tafti and Paul Franken provides an overview of the methods and techniques available for genetic dissection of sleep in mice. Drs. Tafti and Franken emphasize that these techniques can be used in conjunction with established electrophysiological, neuroanatomic, and pharmacological techniques to explore important new areas in sleep physiology. Also in March, a mini-review entitled "Regulation of mammalian circadian clock genes" by Dr. Urs Albrecht explores recent experiments that use genetic and molecular biological tools to lead to a new understanding of the molecular basis of the circadian clock in mammals. Dr. Albrecht's analysis culminates in a working model of the mammalian circadian clock mechanism in the SCN, and he poses the argument that many of the genes and even whole biochemical pathways that make up the circadian clock remain to be discovered.

As with each of the Highlighted Topics series, the Associate Editors and I seek to strengthen awareness of this exciting area of research that touches all of our lives. We also hope that this Highlighted Topics series will provide a stimulus for future studies exploring this area of applied physiology utilizing genetic, molecular, cellular, and integrative approaches. We also hope that this series will promote further discussion and research in this important field. We know that the featured articles in this series only scratch the surface of the complex but intriguing mechanisms underlying the functional genomics of sleep and circadian rhythms. The Associate Editors and I strongly encourage submission of any original research in this exciting area of applied physiology, and this Highlighted Topics series underscores our present and future intent to include this research within the broad scope of the Journal.