A critical role of Ca2+/calmodulin-dependent protein kinase II in coupling between evening and morning circadian oscillators in the suprachiasmatic nucleus

Tomoko Yoshikawa, Ken ichi Honma, Yasufumi Shigeyoshi, Yoko Yamagata, Sato Honma*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

1 被引用数 (Scopus)

抄録

Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) is widely expressed in the brain and is involved in various functions, including memory formation, mood and sleep. We previously reported that CaMKIIα is involved in the circadian molecular clock. Mice lacking functional CaMKIIα (K42R mice) exhibited a gradual increase in activity time (α decompression) of running-wheel (RW) activity due to a lengthened circadian period (τ) of activity offset under constant darkness (DD). In the present study, to investigate the functional roles of CaMKIIα in behavioural rhythms, we measured RW and general movements simultaneously under prolonged DD. Tau became longer as the relative intensity of behaviour activity within an activity time shifted from activity onset towards activity offset. In some K42R mice, α was gradually expanded with a marked reduction of RW activity, while general movements persisted without noticeable decline, which was followed by an abrupt shortening of α (α compression) with differential phase shifts of the activity onset and offset and recovery of RW activity. These results suggest that an internal coupling between the oscillators controlling activity onset and offset is bidirectional but with different strengths. The α compression occurred recurrently in 38% of K42R mice examined with an average interval of 37 days in association with attenuation of RW activity but never in the wild-type (WT) mice. Consistent with behavioural rhythms, the circadian period of the PER2::LUC rhythm in the cultured suprachiasmatic nucleus (SCN) slice was significantly longer in K42R than in WT. These findings are best interpreted by assuming that a loss of functional CaMKIIα attenuates the coupling between the onset and offset oscillators.

本文言語英語
ページ(範囲)3828-3842
ページ数15
ジャーナルEuropean Journal of Neuroscience
60
2
DOI
出版ステータス出版済み - 2024/07

ASJC Scopus 主題領域

  • 神経科学一般

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