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Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
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Related Experiment Videos

Inducing Daytime Circadian Phase Shifts Using Chemogenetic and Spectral Approaches.

Sophie Bass1, Michelle Sun1, Eve Gold1

  • 1Section on Light and Circadian Rhythms, National Institute of Mental Health (NIMH), National Institutes of Health (NIH).

Journal of Visualized Experiments : Jove
|June 29, 2026
PubMed
Summary

Researchers developed new methods to shift circadian rhythms during the day. These techniques, using genetic tools or violet light, allow precise manipulation of the suprachiasmatic nucleus (SCN) for better circadian clock research.

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Area of Science:

  • Chronobiology
  • Neuroscience
  • Molecular Biology

Background:

  • Circadian phase shifting during daytime is limited by reduced photic responsiveness of the suprachiasmatic nucleus (SCN).
  • Existing methods struggle to experimentally manipulate the circadian clock during the day, hindering research into circadian plasticity and photic entrainment.

Purpose of the Study:

  • To develop reliable and temporally precise methods for inducing daytime circadian phase shifts.
  • To enable robust investigation of mechanisms underlying circadian plasticity and photic entrainment during the subjective day.

Main Methods:

  • Chemogenetic strategy using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) delivered intravitreally to activate intrinsically photosensitive retinal ganglion cells (ipRGCs) in mice.
  • Non-invasive wavelength-specific optical stimulation using violet light to exploit ipRGC spectral sensitivity for phase resetting across mammalian systems.

Main Results:

  • Chemogenetic approach enabled controlled activation of the retinohypothalamic pathway, inducing reproducible daytime phase shifts independent of ambient light.
  • Violet light stimulation provided a non-invasive, broadly applicable method for reliable phase resetting during the subjective day without genetic or pharmacological intervention.
  • Protocols for experimental setup, stimulation, validation (locomotor activity), and neuronal activation assessment (c-Fos) are detailed.

Conclusions:

  • Developed versatile tools for inducing daytime circadian phase shifts in mammals.
  • These methods facilitate direct investigation of mechanisms underlying daytime circadian responsiveness and photic entrainment.
  • Advances support research into circadian clock plasticity and regulation.