Abstract

Circadian Clocks (Handbook of Behavioral Neurobiology, Vol. 12) Takahashi, Joseph S., Turek, Fred W. and Moore, Robert Y. (eds) Kluwer Academic/Plenum Publishers 2001 , $175 , 794 pages, ISBN 0-306-46504-3 Most organisms have been forced to adapt to the once-daily rotation of our planet on its axis. The geophysical day–night cycle is not only reflected as circadian (Latin: circa = about, dies = day) rhythms of physiology and behavior, but is also actually incorporated within organisms as a genetically determined temporal program. This endogenous, temperature-compensated timekeeping mechanism recognizes local time, measures its passage, and contributes to the regulation of homeostasis, seasonal behavior, and migration. Evidence for its existence was still being debated as late as 1960, but by 1981 the field had advanced to such a stage that it was reviewed in Volume 4 of the new Handbook of Behavioral Neurobiology. At that time, single gene mutants affecting rhythms in flies and fungi had been isolated, and the suprachiasmatic nucleus (SCN) was being proposed as a candidate circadian clock in mammals, but the terms ‘genetics’, ‘neurotransmitter’, and ‘shift work’ were not yet listed in the index. In the editor's preface, Jürgen Aschoff wrote, ‘The study of the physiological mechanisms underlying circarhythms is a rapidly developing field, and the question of how discrete is the clock from the rest of the body…may soon be answered in the circadian case…’. Twenty years have now passed and our progress has been almost unimaginable. Among other advances, the body of evidence that has identified the SCN as a master circadian pacemaker is so compelling and multidisciplinary that the strength of this functional localization is unsurpassed by that of any other structure in the vertebrate brain. We have discovered intracellular regulatory molecules and biochemical processes that are likely to constitute the actual oscillatory mechanism of the clock. The practical application of our new knowledge has been recognized, and chronobiologists now advise astronauts. Volume 12 of the Handbook, Circadian Clocks, summarizes how extraordinarily far we have come. It is a comprehensive and authoritative reference work of 26 chapters in 6 parts. Included are chapters on entrainment theory and the ecology and evolution of circadian rhythmicity; on the organization of circadian systems, from unicells to invertebrates and non-mammalian and mammalian vertebrates; on the regulation of mammalian rhythmicity, including photic and non-photic entrainment, development and aging, sleep and wakefulness, and seasonality; on cellular and molecular mechanisms in Synechococcus, Gonyaulax, Neurospora, Drosophila, opisthobranch mollusks, and rodents; and on the human circadian system and its role in sleep, performance, aging, affective disorders, endocrine secretion, and photoperiodic responses. The book is handsomely produced and certain to become a manual for molecular biologists, neuroscientists, physiologists, and physicians working on circadian rhythms. While no existing book matches the scope of Circadian Clocks, a few topics are missing even from this volume. Not considered are the clocks of higher plants, or the role of clocks in tidal rhythms and sun compass orientation. There is little, if any, coverage of how circadian rhythms might impact medical practice, i.e. by influencing the timing of pharmacotherapy or the manifestations of disease. Finally, some chapters on molecular mechanisms were apparently written five years ago and are a bit outdated, although the field is moving so fast anyway that it would be impossible for any book to be completely up to date. So, some remarkable new stories – the mutant clock genes responsible for advanced sleep phase syndrome, the role of peripheral oscillators in body rhythmicity, and the identification of candidate circadian photoreceptors and molecules – will need to wait for the next volume. Circadian Clocks clearly shows why the circadian timekeeping system has become such a unique and powerful model for studying genes, brain and behavior. There are remarkable opportunities to begin to understand a biological system at multiple levels of organization, ranging from the regulation of gene expression, to intercellular networks and multisynaptic pathways, and finally to integrated patterns of physiology and performance. Clock investigators include geneticists cloning clock genes, zoologists examining rhythmic behaviors in the wild, neurophysiologists recording spike trains in the hypothalamus, and psychiatrists treating patients with seasonal affective disorder (to name just a few). By enhancing the dialogue between these researchers and their disciplines, Circadian Clocks should serve as a very valuable resource. William J. Schwartz Department of Neurology University of Massachusetts Medical School 55 Lake Ave. North Worcester MA 01655, USA

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