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The Journal of Neuroscience, November 12, 2008, 28(46):11839-11847; doi:10.1523/JNEUROSCI.2191-08.2008

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Behavioral/Systems/Cognitive
Strong Resetting of the Mammalian Clock by Constant Light Followed by Constant Darkness

Rongmin Chen,¹ Dong-oh Seo,¹ Elijah Bell,¹ Charlotte von Gall,² and Choogon Lee¹

¹Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida 32306, and ²Institute of Anatomy II, Johann Wolfgang Goethe University, 60590 Frankfurt, Germany

Correspondence should be addressed to Choogon Lee, Department of Biomedical Sciences, Florida State University, 1115 West Call Street, Tallahassee, FL 32306. Email: Choogon.Lee{at}med.fsu.edu

The mammalian molecular circadian clock in the suprachiasmatic nuclei (SCN) regulates locomotor activity rhythms as well as clocks in peripheral tissues (Reppert and Weaver, 2002; Ko and Takahashi, 2006). Constant light (LL) can induce behavioral and physiological arrhythmicity by desynchronizing clock cells in the SCN (Ohta et al., 2005). We examined how the disordered clock cells resynchronize by probing the molecular clock and measuring behavior in mice transferred from LL to constant darkness (DD). The circadian locomotor activity rhythms disrupted in LL become robustly rhythmic again from the beginning of DD, and the starting phase of the rhythm in DD is specific, not random, suggesting that the desynchronized clock cells are quickly reset in an unconventional manner by the L/D transition. By measuring mPERIOD protein rhythms, we showed that the SCN and peripheral tissue clocks quickly become rhythmic again in phase with the behavioral rhythms. We propose that this resetting mechanism may be different from conventional phase shifting, which involves light induction of Period genes (Albrecht et al., 1997; Shearman et al., 1997; Shigeyoshi et al., 1997). Using our functional insights, we could shift the circadian phase of locomotor activity rhythms by 12 h using a 15 h LL treatment: essentially producing phase reversal by a single light pulse, a feat that has not been reported previously in wild-type mice and that has potential clinical utility.

Key words: circadian rhythms; LL; entrainment; type 0 resetting; PERIOD; suprachiasmatic nuclei; SCN

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Received May 14, 2008; revised Aug. 12, 2008; accepted Sept. 3, 2008.

Correspondence should be addressed to Choogon Lee, Department of Biomedical Sciences, Florida State University, 1115 West Call Street, Tallahassee, FL 32306. Email: Choogon.Lee{at}med.fsu.edu

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