Reciprocity between phase shifts and amplitude changes in the mammalian circadian clock

Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20356-61. doi: 10.1073/pnas.0708877104. Epub 2007 Dec 7.


Circadian rhythms help organisms adapt to predictable daily changes in their environment. Light resets the phase of the underlying oscillator to maintain the organism in sync with its surroundings. Light also affects the amplitude of overt rhythms. At a critical phase during the night, when phase shifts are maximal, light can reduce rhythm amplitude to nearly zero, whereas in the subjective day, when phase shifts are minimal, it can boost amplitude substantially. To explore the cellular basis for this reciprocal relationship between phase shift and amplitude change, we generated a photoentrainable, cell-based system in mammalian fibroblasts that shares several key features of suprachiasmatic nucleus light entrainment. Upon light stimulation, these cells exhibit calcium/cyclic AMP responsive element-binding (CREB) protein phosphorylation, leading to temporally gated acute induction of the Per2 gene, followed by phase-dependent changes in phase and/or amplitude of the PER2 circadian rhythm. At phases near the PER2 peak, photic stimulation causes little phase shift but enhanced rhythm amplitude. At phases near the PER2 nadir, on the other hand, the same stimuli cause large phase shifts but dampen rhythm amplitude. Real-time monitoring of PER2 oscillations in single cells reveals that changes in both synchrony and amplitude of individual oscillators underlie these phenomena.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks* / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Fibroblasts / metabolism
  • Light*
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Period Circadian Proteins
  • Promoter Regions, Genetic
  • Rod Opsins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Cell Cycle Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Nuclear Proteins
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Rod Opsins
  • Transcription Factors
  • melanopsin