Cold-induced suspension and resetting of Ca ²⁺ and transcriptional rhythms in the suprachiasmatic nucleus neurons

Summary

Does the circadian clock keep running under such hypothermic states as daily torpor and hibernation? This fundamental question has been a research subject for decades but has remained unsettled. We addressed this subject by monitoring the circadian rhythm of clock gene transcription and intracellular Ca ²⁺ in the neurons of the suprachiasmatic nucleus (SCN), master circadian clock, in vitro under a cold environment. We discovered that the transcriptional and Ca ²⁺ rhythms are maintained at 22°C–28°C, but suspended at 15°C, accompanied by a large Ca ²⁺ increase. Rewarming instantly resets the Ca ²⁺ rhythms, while transcriptional rhythms reach a stable phase after the transient state and recover their phase relationship with the Ca ²⁺ rhythm. We conclude that SCN neurons remain functional under moderate hypothermia but stop ticking in deep hypothermia and that the rhythms reset after rewarming. These data also indicate that stable Ca ²⁺ oscillation precedes clock gene transcriptional rhythms in SCN neurons.

Graphical abstract

Highlights

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  Transcriptional and Ca ²⁺ rhythms are maintained at 22°C–28°C in SCN neurons

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  Rhythms are suspended at 15°C, accompanied by a large Ca ²⁺ increase

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  Rewarming instantly resets the Ca ²⁺ rhythm

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  Stable Ca ²⁺ rhythm precedes the transcriptional rhythms

Abstract

Biological sciences; Neuroscience; Molecular neuroscience; Cellular neuroscience