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
Affiliations
Ryosuke Enoki
Biophotonics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Division of Biophotonics, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Corresponding author
Naohiro Kon
Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Nagoya 464-8601, Japan; Laboratory of Animal Integrative Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan; Suntory Rising Stars Encouragement Program in Life Sciences (SunRiSE), Suntory Foundation for Life Sciences, Kyoto 619-0284, Japan
Kimiko Shimizu
Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Kenta Kobayashi
School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan
Sota Hiro
Biophotonics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Division of Biophotonics, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan
Ching-Pu Chang
Biophotonics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Division of Biophotonics, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan
Tatsuto Nakane
Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Nagoya 464-8601, Japan
Hirokazu Ishii
Biophotonics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Division of Biophotonics, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan
Joe Sakamoto
Biophotonics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Division of Biophotonics, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan
Yoshifumi Yamaguchi
Hibernation Metabolism, Physiology and Development Group, Institute of Low-Temperature Science, Hokkaido University, Sapporo, Hokkaido, Japan; Graduate School of Environmental Science, Hokkaido University, Sapporo, Hokkaido, Japan; Inamori Research Institute for Science Fellowship (InaRIS), Kyoto, Japan
Tomomi Nemoto
Biophotonics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; Division of Biophotonics, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan; School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan
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 Ca2+ in the neurons of the suprachiasmatic nucleus (SCN), master circadian clock, in vitro under a cold environment. We discovered that the transcriptional and Ca2+ rhythms are maintained at 22°C–28°C, but suspended at 15°C, accompanied by a large Ca2+ increase. Rewarming instantly resets the Ca2+ rhythms, while transcriptional rhythms reach a stable phase after the transient state and recover their phase relationship with the Ca2+ 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 Ca2+ oscillation precedes clock gene transcriptional rhythms in SCN neurons.