Circadian rhythms in isolated brain regions.
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.
Abe
Michikazu
M
National Science Foundation Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, Virginia 22904, USA.
Herzog
Erik D
ED
Yamazaki
Shin
S
Straume
Marty
M
Tei
Hajime
H
Sakaki
Yoshiyuki
Y
Menaker
Michael
M
Block
Gene D
GD
D000818:Animals; D030801:Animals, Genetically Modified; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017930:Genes, Reporter / Q000502:physiology; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000502:physiology*; D009928:Organ Specificity; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D056950:Period Circadian Proteins; D010507:Periodicity; D017440:Photoperiod; D010870:Pineal Gland / Q000187:drug effects / Q000502:physiology; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology; D019076:Transgenes / Q000502:physiology
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D005576:Colforsin; D008156:Luciferases