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Science 337 (6096): 839-842

Copyright © 2012 by the American Association for the Advancement of Science

Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons

Tongfei A. Wang,1,* Yanxun V. Yu,2,*,{dagger} Gubbi Govindaiah,1,3 Xiaoying Ye,3,4,{ddagger} Liana Artinian,1,§ Todd P. Coleman,5 Jonathan V. Sweedler,1,2,3,4 Charles L. Cox,1,2,3 Martha U. Gillette1,2,3,6,||

Abstract: Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day-night cycle. They are orchestrated by a central circadian clock in the brain, the suprachiasmatic nucleus (SCN). Transcription of clock genes is sensitive to metabolic changes in reduction and oxidation (redox); however, circadian cycles in protein oxidation have been reported in anucleate cells, where no transcription occurs. We investigated whether the SCN also expresses redox cycles and how such metabolic oscillations might affect neuronal physiology. We detected self-sustained circadian rhythms of SCN redox state that required the molecular clockwork. The redox oscillation could determine the excitability of SCN neurons through nontranscriptional modulation of multiple potassium (K+) channels. Thus, dynamic regulation of SCN excitability appears to be closely tied to metabolism that engages the clockwork machinery.

1 Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2 Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
3 Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
4 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
5 Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
6 Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.

{ddagger} Present address: The SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA.

§ Present address: Department of Biology, Georgia State University, Atlanta, GA 30302–4010, USA.

|| To whom correspondence should be addressed. E-mail: mgillett{at}illinois.edu


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