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Measuring Relative Coupling Strength in Circadian Systems.

Christoph Schmal1, Erik D Herzog2, Hanspeter Herzel3

  • 1Institute for Theoretical Biology, Charité-Universitätsmedizin, Berlin, Germany.

Journal of Biological Rhythms
|December 9, 2017
PubMed
Summary

We developed a new method to measure the coupling strength of circadian rhythms in cells by analyzing period and phase distributions. This approach helps understand how cellular rhythms synchronize and impact physiological functions.

Keywords:
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Area of Science:

  • Chronobiology
  • Systems Biology
  • Biophysics

Background:

  • Single-cell imaging reveals cellular circadian rhythms, which can synchronize to orchestrate tissue-level physiological outputs.
  • Quantifying the coupling strength between these cellular oscillators is challenging, especially concerning factors like cell density, genetic modifications, and drug treatments.

Purpose of the Study:

  • To develop and validate a method for quantifying the relative coupling strength in ensembles of circadian oscillators.
  • To investigate how coupling strength influences oscillator network dynamics, including period, phase, and amplitude distributions.

Main Methods:

  • Simulated different oscillator networks to analyze the relationship between coupling strength and statistical distributions of period, phase, and amplitude.
  • Applied the developed method to analyze experimental data of PERIOD2 expression in suprachiasmatic nucleus slices treated with tetrodotoxin (TTX).
  • Validated findings by analyzing an oscillator network derived directly from experimental data.

Main Results:

  • Simulations showed that narrower period and phase distributions, along with potential amplitude increases due to resonance, correlate with increased coupling strength.
  • Variances in periods and phases monotonically decrease with increasing coupling strength, serving as reliable measures.
  • Analysis of TTX-treated suprachiasmatic nucleus slices indicated a reduction in coupling strength, consistent with theoretical predictions.

Conclusions:

  • The proposed method, analyzing period, phase, and amplitude distributions, effectively quantifies relative coupling strength in circadian oscillator networks.
  • Tetrodotoxin (TTX) treatment appears to reduce coupling strength in the suprachiasmatic nucleus.
  • This approach is broadly applicable to various biological systems, including fibroblast and hepatocyte networks, and social synchronization in different species.