The choroid plexus is an important circadian clock component

Jihwan Myung,Yoshiaki Tsukizawa,Yong Zhang,Michael J Holtzman,Hanspeter Herzel,Erik De Schutter,Christoph Schmal,Toru Takumi,Pia Rose,Sungho Hong,Grigory Bordyugov

doi:10.1038/s41467-018-03507-2

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.

Highlights

choroid plexus (CP) clock adjusts the suprachiasmatic nucleus (SCN) clock likely via circulation of cerebrospinal fluid, finely tuning behavioral circadian rhythms
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
Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal[1] gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, finely tuning behavioral circadian rhythms

Summary

Introduction

CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, finely tuning behavioral circadian rhythms. 2 Computational Neuroscience Unit, Okinawa Institute of Science and Technology, Okinawa. These authors contributed : Jihwan Myung, Christoph Schmal, Sungho Hong. The SCN is an encoder of seasonal rhythms through phase reorganization among its subregions, in adaptation to daylength[1,2,3]. It propagates information of these external cycles to a web of internal circadian cycles in peripheral circadian clocks[4]. A long daylength causes phase reorganization among peripheral circadian clocks in the body, to SCN subregions[5]. The CVOs share a common structure of a tight junctionprotected epithelial cell layer (blood–CSF barrier, BCSFB)

Methods

Results

Conclusion