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Circadian Rhythms and Gene Regulation02:19

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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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Defining Clock Neurons Within Distributed Circadian Circuits Through Multiscale Technologies.

Burgundy Walters1, Shubham Garg2, Diego C Fernandez2,3

  • 1Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, Ohio.

Journal of Biological Rhythms
|May 23, 2026
PubMed
Summary
This summary is machine-generated.

This study redefines circadian clock neurons beyond the master pacemaker. It proposes four criteria to identify these neurons across the brain, essential for understanding circadian organization and treating sleep disorders.

Keywords:
circadian disruptioncircadian rhythmsclock neuronsdistributed circadian circuitsextra-SCN clocksneurological disorderssuprachiasmatic nucleus (SCN)

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Area of Science:

  • Neuroscience
  • Chronobiology
  • Molecular Biology

Background:

  • The traditional view of the mammalian circadian system is a hierarchy with the suprachiasmatic nucleus (SCN) as the master pacemaker.
  • Recent molecular and circuit studies reveal a more complex, distributed network of circadian clock neurons beyond the SCN.
  • This challenges the classical central-peripheral model of circadian regulation.

Purpose of the Study:

  • To synthesize recent findings on molecular, cellular, and systems-level studies of brain circadian clocks.
  • To propose an operational framework for identifying circadian clock neurons across brain circuits.
  • To clarify the defining features of neurons within brain circadian clocks.

Main Methods:

  • Integration of high-resolution molecular profiling with functional circuit analysis.
  • Review of molecular, cellular, and systems-level studies.
  • Application of multiscale approaches including single-cell transcriptomics and causal circuit manipulation.

Main Results:

  • Identified multiple brain regions outside the SCN containing neurons with intrinsic circadian properties.
  • Proposed four defining criteria for circadian clock neurons: molecular oscillation, autonomy, physiological rhythmicity, and circuit influence.
  • Highlighted how multiscale approaches are reshaping the understanding of brain circadian organization.

Conclusions:

  • The classical central-peripheral model is insufficient to describe the complexity of brain circadian organization.
  • An operational framework with four criteria aids in identifying circadian clock neurons.
  • Clarifying clock neuron identity is crucial for mapping distributed circadian circuits and developing interventions for circadian and sleep disruption disorders.