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Parameterized resetting model captures dose-dependent entrainment of the mouse circadian clock

Author

Listed:
  • Kosaku Masuda

    (University of Tsukuba
    University of Tsukuba)

  • Ryusuke Yoshimoto

    (University of Tsukuba
    University of Tsukuba)

  • Ruoshi Li

    (University of Tsukuba
    University of Tsukuba)

  • Takeshi Sakurai

    (University of Tsukuba
    University of Tsukuba
    University of Tsukuba)

  • Arisa Hirano

    (University of Tsukuba
    University of Tsukuba)

Abstract

The phase response curve (PRC) represents the time-dependent changes in circadian rhythm phase following internal or external stimuli. However, this time dependence complicates PRC measurement and quantification owing to its variable shape with changing stimulus intensity. Our previous work demonstrated that resetting a desynchronized circadian clock (singularity response, SR) simplifies the analysis by requiring only amplitude and phase parameters. In this study, we construct a comprehensive model for phase resetting in the mouse circadian clock by converting PRCs into SR parameters. We analyze single-cell PRCs and show that the SR amplitude parameters for different stimulus concentrations follow the Hill equation. Additionally, the model predicts the combined effects of multiple stimuli and pre-treatment (background) on phase response by simple addition or subtraction of individual SR parameters. Experimental validation using SR measurements in mouse cells and tissues confirms the model’s accuracy. This study demonstrates that SRs facilitate PRC quantification and reveal simple rules governing phase resetting properties under various conditions using SR parameters.

Suggested Citation

  • Kosaku Masuda & Ryusuke Yoshimoto & Ruoshi Li & Takeshi Sakurai & Arisa Hirano, 2025. "Parameterized resetting model captures dose-dependent entrainment of the mouse circadian clock," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56792-z
    DOI: 10.1038/s41467-025-56792-z
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    References listed on IDEAS

    as
    1. Satoshi Koinuma & Hiroshi Kori & Isao T Tokuda & Kazuhiro Yagita & Yasufumi Shigeyoshi, 2017. "Transition of phase response properties and singularity in the circadian limit cycle of cultured cells," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-16, July.
    2. Kosaku Masuda & Naohiro Kon & Kosuke Iizuka & Yoshitaka Fukada & Takeshi Sakurai & Arisa Hirano, 2023. "Singularity response reveals entrainment properties in mammalian circadian clock," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Kosaku Masuda & Isao T. Tokuda & Norihito Nakamichi & Hirokazu Fukuda, 2021. "The singularity response reveals entrainment properties of the plant circadian clock," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    4. Gal Manella & Dan Aizik & Rona Aviram & Marina Golik & Gad Asher, 2021. "Circa-SCOPE: high-throughput live single-cell imaging method for analysis of circadian clock resetting," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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