We congratulate Dr. Jihwan Myung on his forthcoming publication in Nature Communications!
Title: The Choroid Plexus is an Oscillator and Regulates Behavioral Circadian Rhythm
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 non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discover 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 co-culture model and in vivotargeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock probably adjusts the SCN clock via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.
The work challenges the traditional notion of hierarchical organization of circadian clocks, which states the bodily circadian rhythms are coordinated by one center, the suprachiasmatic nucleus (SCN). It shows that the choroid plexus (CP) is a large tissue of circadian clocks (left, Bmal1 expression in the mouse brain), that provides retrograde feedback to the SCN and adjusts behavioral rhythms (right, actograms). The study is a result of international collaborations with RIKEN Brain Science Institute and Okinawa Institute of Science and Technology (Japan), Humboldt University and Charité (Germany), and Washington University in St. Louis (United States).