Defining Clock Neurons Within Distributed Circadian Circuits Through Multiscale Technologies

Four criteria are proposed to characterize circadian clock neurons: molecular oscillation, autonomy, physiological rhythmicity, and circuit influence.

• The mammalian circadian system is more complex than the traditional hierarchical model centered on the suprachiasmatic nucleus (SCN).
• Neurons outside the SCN have intrinsic circadian properties and contribute to processing temporal information.
• Recent studies integrate molecular profiling and circuit analysis to redefine the characteristics of clock neurons.
• The proposed operational framework aims to identify clock neurons across different brain circuits.
• Multiscale approaches, including single-cell transcriptomics and causal circuit manipulation, are enhancing the understanding of circadian organization in the brain.

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