Quantification of circadian rhythms in single cells

PLoS Comput Biol. 2009 Nov;5(11):e1000580. doi: 10.1371/journal.pcbi.1000580. Epub 2009 Nov 26.


Bioluminescence techniques allow accurate monitoring of the circadian clock in single cells. We have analyzed bioluminescence data of Per gene expression in mouse SCN neurons and fibroblasts. From these data, we extracted parameters such as damping rate and noise intensity using two simple mathematical models, one describing a damped oscillator driven by noise, and one describing a self-sustained noisy oscillator. Both models describe the data well and enabled us to quantitatively characterize both wild-type cells and several mutants. It has been suggested that the circadian clock is self-sustained at the single cell level, but we conclude that present data are not sufficient to determine whether the circadian clock of single SCN neurons and fibroblasts is a damped or a self-sustained oscillator. We show how to settle this question, however, by testing the models' predictions of different phases and amplitudes in response to a periodic entrainment signal (zeitgeber).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks / physiology*
  • CLOCK Proteins / physiology*
  • Circadian Rhythm / physiology*
  • Fibroblasts / physiology*
  • Gene Expression Regulation / physiology*
  • Luminescent Measurements / methods*
  • Mice
  • Neurons / physiology*


  • CLOCK Proteins