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Nat Commun. 2018 Mar 14;9(1):1062. doi: 10.1038/s41467-018-03507-2.

The choroid plexus is an important circadian clock component.

Author information

1
RIKEN Brain Science Institute (BSI), Wako, 351-0198, Japan. jhmyung@gmail.com.
2
Computational Neuroscience Unit, Okinawa Institute of Science and Technology, Okinawa, 904-0495, Japan. jhmyung@gmail.com.
3
Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, 11031, Taiwan. jhmyung@gmail.com.
4
TMU-Research Center of Brain and Consciousness, Taipei Medical University, Taipei, 11031, Taiwan. jhmyung@gmail.com.
5
Laboratory of Braintime, Shuang Ho Hospital, New Taipei City, 23561, Taiwan. jhmyung@gmail.com.
6
Institute for Theoretical Biology, Charité-Universitätsmedizin and Humboldt Universität, Berlin, D-10115, Germany.
7
Computational Neuroscience Unit, Okinawa Institute of Science and Technology, Okinawa, 904-0495, Japan.
8
Department of Anatomy, Hiroshima University School of Medicine, Hiroshima, 734-8551, Japan.
9
Pulmonary and Clinical Care Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
10
Institute for Theoretical Biology, Charité-Universitätsmedizin and Humboldt Universität, Berlin, D-10115, Germany. h.herzel@biologie.hu-berlin.de.
11
RIKEN Brain Science Institute (BSI), Wako, 351-0198, Japan. toru.takumi@riken.jp.
12
Department of Anatomy, Hiroshima University School of Medicine, Hiroshima, 734-8551, Japan. toru.takumi@riken.jp.

Abstract

Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of "twist" circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.

PMID:
29540683
PMCID:
PMC5852131
DOI:
10.1038/s41467-018-03507-2
[Indexed for MEDLINE]
Free PMC Article

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