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The Journal of Neuroscience, January 1, 2002, 22(1):350-356
Circadian Rhythms in Isolated Brain Regions
Michikazu Abe1, *, Erik D. Herzog1, *, Shin Yamazaki1, Marty Straume1, Hajime Tei2, Yoshiyuki Sakaki2, Michael Menaker1, and Gene D. Block1 1 National Science Foundation Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, Virginia 22904, and 2 Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus has been referred to as the master circadian pacemaker that drives daily rhythms in behavior and physiology. There is, however, evidence for extra-SCN circadian oscillators. Neural tissues cultured from rats carrying the Per-luciferase transgene were used to monitor the intrinsic Per1 expression patterns in different brain areas and their response to changes in the light cycle. Although many Per-expressing brain areas were arrhythmic in culture, 14 of the 27 areas examined were rhythmic. The pineal and pituitary glands both expressed rhythms that persisted for >3 d in vitro, with peak expression during the subjective night. Nuclei in the olfactory bulb and the ventral hypothalamus expressed rhythmicity with peak expression at night, whereas other brain areas were either weakly rhythmic and peaked at night, or arrhythmic. After a 6 hr advance or delay in the light cycle, the pineal, paraventricular nucleus of the hypothalamus, and arcuate nucleus each adjusted the phase of their rhythmicity with different kinetics. Together, these results indicate that the brain contains multiple, damped circadian oscillators outside the SCN. The phasing of these oscillators to one another may play a critical role in coordinating brain activity and its adjustment to changes in the light cycle.
Key words: suprachiasmatic nucleus; pineal; pituitary; olfactory bulb; arcuate nucleus; Per; luciferase; entrainment; jet lag
* M.A. and E.D.H. contributed equally to this work.Correspondence should be addressed to Gene Block, Gilmer Hall, Department of Biology, University of Virginia, Charlottesville, VA 22904. E-mail: gdb{at}virginia.edu.
M. Abe's present address: Research Laboratory I, Mitsubishi Pharma Corp., Yokohama 227-0033, Japan.
E. D. Herzog's present address: Department of Biology, Washington University, St. Louis, MO 63130.
Copyright © 2002 Society for Neuroscience 0270-6474/02/221350-07$05.00/0
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