Cold-induced suspension and resetting of Ca2+ and transcriptional rhythms in the suprachiasmatic nucleus neurons
Ryosuke Enoki, Naohiro Kon, Kimiko Shimizu, Kenta Kobayashi, Sota Hiro, Ching-Pu Chang, Tatsuto Nakane, Hirokazu Ishii, Joe Sakamoto, Yoshifumi Yamaguchi, Tomomi Nemoto
Abstract
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.