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Topological specificity and hierarchical network of the circadian calcium rhythm in the suprachiasmatic nucleus.

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Title: Topological specificity and hierarchical network of the circadian calcium rhythm in the suprachiasmatic nucleus.
Authors: Enoki, Ryosuke Browse this author →KAKEN DB
Kuroda, Shigeru Browse this author
Ono, Daisuke Browse this author
Hasan, Mazahir T Browse this author
Ueda, Tetsuo Browse this author
Honma, Sato Browse this author →KAKEN DB
Honma, Ken-Ichi Browse this author
Issue Date: 26-Dec-2012
Publisher: National Academy of Sciences
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 109
Issue: 52
Start Page: 21498
End Page: 21503
Publisher DOI: 10.1073/pnas.1214415110
PMID: 23213253
Abstract: The circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is a hierarchical multioscillator system in which neuronal networks play crucial roles in expressing coherent rhythms in physiology and behavior. However, our understanding of the neuronal network is still incomplete. Intracellular calcium mediates the input signals, such as phase-resetting stimuli, to the core molecular loop involving clock genes for circadian rhythm generation and the output signals from the loop to various cellular functions, including changes in neurotransmitter release. Using a unique large-scale calcium imaging method with genetically encoded calcium sensors, we visualized intracellular calcium from the entire surface of SCN slice in culture including the regions where autonomous clock gene expression was undetectable. We found circadian calcium rhythms at a single-cell level in the SCN, which were topologically specific with a larger amplitude and more delayed phase in the ventral region than the dorsal. The robustness of the rhythm was reduced but persisted even after blocking the neuronal firing with tetrodotoxin (TTX). Notably, TTX dissociated the circadian calcium rhythms between the dorsal and ventral SCN. In contrast, a blocker of gap junctions, carbenoxolone, had only a minor effect on the calcium rhythms at both the single-cell and network levels. These results reveal the topological specificity of the circadian calcium rhythm in the SCN and the presence of coupled regional pacemakers in the dorsal and ventral regions. Neuronal firings are not necessary for the persistence of the calcium rhythms but indispensable for the hierarchical organization of rhythmicity in the SCN.
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 榎木 亮介

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