The choroid plexus is an important circadian clock component

J. Myung, C. Schmal, S. Hong, Y. Tsukizawa, P. Rose, Y. Zhang, M.J. Holtzman, E. De Schutter, H. Herzel, G. Bordyugov, T. Takumi

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Article number1062
Pages (from-to)1062
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Circadian Clocks
Choroid Plexus
clocks
Suprachiasmatic Nucleus
Clocks
nuclei
loci
brain
Brain
Gene Deletion
Periodicity
Circadian Rhythm
Coculture Techniques
circadian rhythms
hypothalamus
cerebrospinal fluid
Hypothalamus
Cerebrospinal fluid
Cerebrospinal Fluid
deletion

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Myung, J., Schmal, C., Hong, S., Tsukizawa, Y., Rose, P., Zhang, Y., ... Takumi, T. (2018). The choroid plexus is an important circadian clock component. Nature Communications, 9(1), 1062. [1062]. https://doi.org/10.1038/s41467-018-03507-2

The choroid plexus is an important circadian clock component. / Myung, J.; Schmal, C.; Hong, S.; Tsukizawa, Y.; Rose, P.; Zhang, Y.; Holtzman, M.J.; De Schutter, E.; Herzel, H.; Bordyugov, G.; Takumi, T.

In: Nature Communications, Vol. 9, No. 1, 1062, 01.12.2018, p. 1062.

Research output: Contribution to journalArticle

Myung, J, Schmal, C, Hong, S, Tsukizawa, Y, Rose, P, Zhang, Y, Holtzman, MJ, De Schutter, E, Herzel, H, Bordyugov, G & Takumi, T 2018, 'The choroid plexus is an important circadian clock component', Nature Communications, vol. 9, no. 1, 1062, pp. 1062. https://doi.org/10.1038/s41467-018-03507-2
Myung J, Schmal C, Hong S, Tsukizawa Y, Rose P, Zhang Y et al. The choroid plexus is an important circadian clock component. Nature Communications. 2018 Dec 1;9(1):1062. 1062. https://doi.org/10.1038/s41467-018-03507-2
Myung, J. ; Schmal, C. ; Hong, S. ; Tsukizawa, Y. ; Rose, P. ; Zhang, Y. ; Holtzman, M.J. ; De Schutter, E. ; Herzel, H. ; Bordyugov, G. ; Takumi, T. / The choroid plexus is an important circadian clock component. In: Nature Communications. 2018 ; Vol. 9, No. 1. pp. 1062.
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title = "The choroid plexus is an important circadian clock component",
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.",
author = "J. Myung and C. Schmal and S. Hong and Y. Tsukizawa and P. Rose and Y. Zhang and M.J. Holtzman and {De Schutter}, E. and H. Herzel and G. Bordyugov and T. Takumi",
note = "Export Date: 18 September 2018 通訊地址: Myung, J.; RIKEN Brain Science Institute (BSI)Japan; 電子郵件: jhmyung@gmail.com 參考文獻: Evans, J.A., Leise, T.L., Castanon-Cervantes, O., Davidson, A.J., Dynamic interactions mediated by nonredundant signaling mechanisms couple circadian clock neurons (2013) Neuron, 80, pp. 973-983; Myung, J., GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time (2015) Proc. Natl Acad. Sci. USA, 112, pp. E3920-E3929; Azzi, A., Network dynamics mediate circadian clock plasticity (2017) Neuron, 93, pp. 441-450; Dibner, C., Schibler, U., Albrecht, U., The mammalian circadian timing system: Organization and coordination of central and peripheral clocks (2010) Annu. Rev. Physiol., 72, pp. 517-549; Evans, J.A., Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body (2015) BMC Biol., 13, p. 43; Herzog, E.D., Tosini, G., The mammalian circadian clock shop (2001) Semin. Cell. Dev. Biol., 12, pp. 295-303; Pauls, S.D., Honma, K., Honma, S., Silver, R., Deconstructing circadian rhythmicity with models and manipulations (2016) Trends Neurosci., 39, pp. 405-419; Quintela, T., Sousa, C., Patriarca, F.M., Goncalves, I., Santos, C.R., Gender associated circadian oscillations of the clock genes in rat choroid plexus (2015) Brain. Struct. Funct., 220, pp. 1251-1262; Quintela, T., The choroid plexus harbors a circadian oscillator modulated by estrogens (2018) Chronobiol. Int., 35, pp. 270-279; Brinker, T., Stopa, E., Morrison, J., Klinge, P., A new look at cerebrospinal fluid circulation (2014) Fluids Barriers CNS, 11, p. 10; Nilsson, C., Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging (1992) Am. J. Physiol., 262, pp. R20-R24; Sakka, L., Coll, G., Chazal, J., Anatomy and physiology of cerebrospinal fluid (2011) Eur. Ann. Otorhinolaryngol. Head Neck Dis., 128, pp. 309-316; Iliff, J.J., A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta (2012) Sci. Transl. Med., 4, p. 147ra111; Xie, L., Sleep drives metabolite clearance from the adult brain (2013) Science, 342, pp. 373-377; Moore-Ede, M.C., Physiology of the circadian timing system: Predictive versus reactive homeostasis (1986) Am. J. Physiol., 250, pp. R737-R752; Noguchi, T., Dual-color luciferase mouse directly demonstrates coupled expression of two clock genes (2010) Biochemistry, 49, pp. 8053-8061; Yamazaki, S., Resetting central and peripheral circadian oscillators in transgenic rats (2000) Science, 288, pp. 682-685; Yoo, S.H., PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues (2004) Proc. Natl Acad. Sci. USA, 101, pp. 5339-5346; Zhang, R., Lahens, N.F., Ballance, H.I., Hughes, M.E., Hogenesch, J.B., A circadian gene expression atlas in mammals: Implications for biology and medicine (2014) Proc. Natl Acad. Sci. USA, 111, pp. 16219-16224; Guilding, C., Hughes, A.T., Brown, T.M., Namvar, S., Piggins, H.D., A riot of rhythms: Neuronal and glial circadian oscillators in the mediobasal hypothalamus (2009) Mol. Brain, 2, p. 28; Park, J.S., Identification of a circadian clock in the inferior colliculus and its dysregulation by noise exposure (2016) J. Neurosci., 36, pp. 5509-5519; Mendoza, J., Pevet, P., Felder-Schmittbuhl, M.P., Bailly, Y., Challet, E., The cerebellum harbors a circadian oscillator involved in food anticipation (2010) J. Neurosci., 30, pp. 1894-1904; Lun, M.P., Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production (2015) J. Neurosci., 35, pp. 4903-4916; Myung, J., Pauls, S.D., Encoding seasonal information in a two-oscillator model of the multi-oscillator circadian clock (2017) Eur. J. Neurosci., , https://doi.org/10.1111/ejn.13697; Benninger, R.K., Zhang, M., Head, W.S., Satin, L.S., Piston, D.W., Gap junction coupling and calcium waves in the pancreatic islet (2008) Biophys. J., 95, pp. 5048-5061; Marques, F., Transcriptome signature of the adult mouse choroid plexus (2011) Fluids Barriers CNS, 8, p. 10; Liddelow, S.A., Mechanisms that determine the internal environment of the developing brain: A transcriptomic, functional and ultrastructural approach (2013) PLoS ONE, 8, p. e65629; Huang, T., Foxj1 is required for apical localization of ezrin in airway epithelial cells (2003) J. Cell Sci., 116, pp. 4935-4945; Gonze, D., Bernard, S., Waltermann, C., Kramer, A., Herzel, H., Spontaneous synchronization of coupled circadian oscillators (2005) Biophys. J., 89, pp. 120-129; Kim, J.K., Kilpatrick, Z.P., Bennett, M.R., Josic, K., Molecular mechanisms that regulate the coupled period of the mammalian circadian clock (2014) Biophys. J., 106, pp. 2071-2081; Gonze, D., Modeling circadian clocks: From equations to oscillations (2011) Cent. Eur. J. Biol., 6, pp. 699-711; Roenneberg, T., Chua, E.J., Bernardo, R., Mendoza, E., Modelling biological rhythms (2008) Curr. Biol., 18, pp. R826-R835; Schmal, C., Herzog, E.D., Herzel, H., Measuring relative coupling strength in circadian systems (2018) J. Biol. Rhythms, 33 (1), pp. 84-98; Glass, L., Mackey, M.C., (1988) From Clocks to Chaos: The Rhythms of Life, , Princeton University Press, Princeton, NJ; Abraham, U., Coupling governs entrainment range of circadian clocks (2010) Mol. Syst. Biol., 6, p. 438; Ashwin, P., Coombes, S., Nicks, R., Mathematical frameworks for oscillatory network dynamics in neuroscience (2016) J. Math. Neurosci., 6, p. 2; Schmal, C., Myung, J., Herzel, H., Bordyugov, G., Moran's i quantifies spatiotemporal pattern formation in neural imaging data (2017) Bioinformatics, 33, pp. 3072-3079; Granada, A.E., Bordyugov, G., Kramer, A., Herzel, H., Human chronotypes from a theoretical perspective (2013) PLoS ONE, 8, p. e59464; Pan, F., Mills, S.L., Massey, S.C., Screening of gap junction antagonists on dye coupling in the rabbit retina (2007) Vis. Neurosci., 24, pp. 609-618; Ono, D., Honma, S., Honma, K., Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus (2013) Nat. Commun., 4, p. 1666; Balsalobre, A., Resetting of circadian time in peripheral tissues by glucocorticoid signaling (2000) Science, 289, pp. 2344-2347; Maywood, E.S., Chesham, J.E., O'Brien, J.A., Hastings, M.H., A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits (2011) Proc. Natl Acad. Sci. USA, 108, pp. 14306-14311; Myung, J., Period coding of Bmal1 oscillators in the suprachiasmatic nucleus (2012) J. Neurosci., 32, pp. 8900-8918; Hofstetter, J.R., Mayeda, A.R., Possidente, B., Nurnberger, J.I., Jr., Quantitative trait loci (QTL) for circadian rhythms of locomotor activity in mice (1995) Behav. Genet., 25, pp. 545-556; Ono, D., Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus in parallel with behavioral outputs (2017) Proc. Natl Acad. Sci. USA, 114, pp. E3699-E3708; Zhang, Y., A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cells (2007) Am. J. Respir. Cell Mol. Biol., 36, pp. 515-519; Hara, M., Robust circadian clock oscillation and osmotic rhythms in inner medulla reflecting cortico-medullary osmotic gradient rhythm in rodent kidney (2017) Sci. Rep., 7, p. 7306; Lun, M.P., Monuki, E.S., Lehtinen, M.K., Development and functions of the choroid plexus-cerebrospinal fluid system (2015) Nat. Rev. Neurosci., 16, pp. 445-457; Vansteensel, M.J., Dissociation between circadian Per1 and neuronal and behavioral rhythms following a shifted environmental cycle (2003) Curr. Biol., 13, pp. 1538-1542; Kiessling, S., Eichele, G., Oster, H., Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag (2010) J. Clin. Invest., 120, pp. 2600-2609; Tso, C.F., Astrocytes regulate daily rhythms in the suprachiasmatic nucleus and behavior (2017) Curr. Biol., 27, pp. 1055-1061; Brancaccio, M., Patton, A.P., Chesham, J.E., Maywood, E.S., Hastings, M.H., Astrocytes control circadian timekeeping in the suprachiasmatic nucleus via glutamatergic signaling (2017) Neuron, 93, pp. 1420e1425-1435e1425; Barca-Mayo, O., Astrocyte deletion of Bmal1 alters daily locomotor activity and cognitive functions via GABA signalling (2017) Nat. Commun., 8, p. 14336; Bernard, S., Gonze, D., Cajavec, B., Herzel, H., Kramer, A., Synchronizationinduced rhythmicity of circadian oscillators in the suprachiasmatic nucleus (2007) PLoS. Comput. Biol., 3, p. e68; Gomez-Gardenes, J., Gomez, S., Arenas, A., Moreno, Y., Explosive synchronization transitions in scale-free networks (2011) Phys. Rev. Lett., 106, p. 128701; Zhang, X., Hu, X., Kurths, J., Liu, Z., Explosive synchronization in a general complex network (2013) Phys. Rev. e Stat. Nonlin. Soft Matter Phys., 88, p. 010802; Meeker, K., Wavelet measurement suggests cause of period instability in mammalian circadian neurons (2011) J. Biol. Rhythms, 26, pp. 353-362; Jovanova-Nesic, K., Choroid plexus connexin 43 expression and gap junction flexibility are associated with clinical features of acute EAE (2009) Ann. N. Y. Acad. Sci., 1173, pp. 75-82; Negoro, H., Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm (2012) Nat. Commun., 3, p. 809; Haas, J.S., Zavala, B., Landisman, C.E., Activity-dependent long-term depression of electrical synapses (2011) Science, 334, pp. 389-393; De Bock, M., A new angle on blood-CNS interfaces: A role for connexins? (2014) FEBS Lett., 588, pp. 1259-1270; Hughes, A.T., Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC2-signaling deficient mice (2015) Sci. Rep., 5, p. 14044; St John, P.C., Doyle, F.J., Quantifying stochastic noise in cultured circadian reporter cells (2015) PLoS. Comput. Biol., 11, p. e1004451; Leise, T.L., Harrington, M.E., Wavelet-based time series analysis of circadian rhythms (2011) J. Biol. Rhythms, 26, pp. 454-463; Winfree, A.T., (2001) The Geometry of Biological Time, 2. , Springer, New York, NY; Schmal, C., Myung, J., Herzel, H., Bordyugov, G., A theoretical study on seasonality (2015) Front. Neurol., 6, p. 94",
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TY - JOUR

T1 - The choroid plexus is an important circadian clock component

AU - Myung, J.

AU - Schmal, C.

AU - Hong, S.

AU - Tsukizawa, Y.

AU - Rose, P.

AU - Zhang, Y.

AU - Holtzman, M.J.

AU - De Schutter, E.

AU - Herzel, H.

AU - Bordyugov, G.

AU - Takumi, T.

N1 - Export Date: 18 September 2018 通訊地址: Myung, J.; RIKEN Brain Science Institute (BSI)Japan; 電子郵件: jhmyung@gmail.com 參考文獻: Evans, J.A., Leise, T.L., Castanon-Cervantes, O., Davidson, A.J., Dynamic interactions mediated by nonredundant signaling mechanisms couple circadian clock neurons (2013) Neuron, 80, pp. 973-983; Myung, J., GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time (2015) Proc. Natl Acad. Sci. USA, 112, pp. E3920-E3929; Azzi, A., Network dynamics mediate circadian clock plasticity (2017) Neuron, 93, pp. 441-450; Dibner, C., Schibler, U., Albrecht, U., The mammalian circadian timing system: Organization and coordination of central and peripheral clocks (2010) Annu. Rev. Physiol., 72, pp. 517-549; Evans, J.A., Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body (2015) BMC Biol., 13, p. 43; Herzog, E.D., Tosini, G., The mammalian circadian clock shop (2001) Semin. Cell. Dev. Biol., 12, pp. 295-303; Pauls, S.D., Honma, K., Honma, S., Silver, R., Deconstructing circadian rhythmicity with models and manipulations (2016) Trends Neurosci., 39, pp. 405-419; Quintela, T., Sousa, C., Patriarca, F.M., Goncalves, I., Santos, C.R., Gender associated circadian oscillations of the clock genes in rat choroid plexus (2015) Brain. Struct. Funct., 220, pp. 1251-1262; Quintela, T., The choroid plexus harbors a circadian oscillator modulated by estrogens (2018) Chronobiol. Int., 35, pp. 270-279; Brinker, T., Stopa, E., Morrison, J., Klinge, P., A new look at cerebrospinal fluid circulation (2014) Fluids Barriers CNS, 11, p. 10; Nilsson, C., Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging (1992) Am. J. Physiol., 262, pp. R20-R24; Sakka, L., Coll, G., Chazal, J., Anatomy and physiology of cerebrospinal fluid (2011) Eur. Ann. Otorhinolaryngol. Head Neck Dis., 128, pp. 309-316; Iliff, J.J., A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta (2012) Sci. Transl. Med., 4, p. 147ra111; Xie, L., Sleep drives metabolite clearance from the adult brain (2013) Science, 342, pp. 373-377; Moore-Ede, M.C., Physiology of the circadian timing system: Predictive versus reactive homeostasis (1986) Am. J. Physiol., 250, pp. R737-R752; Noguchi, T., Dual-color luciferase mouse directly demonstrates coupled expression of two clock genes (2010) Biochemistry, 49, pp. 8053-8061; Yamazaki, S., Resetting central and peripheral circadian oscillators in transgenic rats (2000) Science, 288, pp. 682-685; Yoo, S.H., PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues (2004) Proc. Natl Acad. Sci. USA, 101, pp. 5339-5346; Zhang, R., Lahens, N.F., Ballance, H.I., Hughes, M.E., Hogenesch, J.B., A circadian gene expression atlas in mammals: Implications for biology and medicine (2014) Proc. Natl Acad. Sci. USA, 111, pp. 16219-16224; Guilding, C., Hughes, A.T., Brown, T.M., Namvar, S., Piggins, H.D., A riot of rhythms: Neuronal and glial circadian oscillators in the mediobasal hypothalamus (2009) Mol. Brain, 2, p. 28; Park, J.S., Identification of a circadian clock in the inferior colliculus and its dysregulation by noise exposure (2016) J. Neurosci., 36, pp. 5509-5519; Mendoza, J., Pevet, P., Felder-Schmittbuhl, M.P., Bailly, Y., Challet, E., The cerebellum harbors a circadian oscillator involved in food anticipation (2010) J. Neurosci., 30, pp. 1894-1904; Lun, M.P., Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production (2015) J. Neurosci., 35, pp. 4903-4916; Myung, J., Pauls, S.D., Encoding seasonal information in a two-oscillator model of the multi-oscillator circadian clock (2017) Eur. J. Neurosci., , https://doi.org/10.1111/ejn.13697; Benninger, R.K., Zhang, M., Head, W.S., Satin, L.S., Piston, D.W., Gap junction coupling and calcium waves in the pancreatic islet (2008) Biophys. J., 95, pp. 5048-5061; Marques, F., Transcriptome signature of the adult mouse choroid plexus (2011) Fluids Barriers CNS, 8, p. 10; Liddelow, S.A., Mechanisms that determine the internal environment of the developing brain: A transcriptomic, functional and ultrastructural approach (2013) PLoS ONE, 8, p. e65629; Huang, T., Foxj1 is required for apical localization of ezrin in airway epithelial cells (2003) J. Cell Sci., 116, pp. 4935-4945; Gonze, D., Bernard, S., Waltermann, C., Kramer, A., Herzel, H., Spontaneous synchronization of coupled circadian oscillators (2005) Biophys. J., 89, pp. 120-129; Kim, J.K., Kilpatrick, Z.P., Bennett, M.R., Josic, K., Molecular mechanisms that regulate the coupled period of the mammalian circadian clock (2014) Biophys. J., 106, pp. 2071-2081; Gonze, D., Modeling circadian clocks: From equations to oscillations (2011) Cent. Eur. J. Biol., 6, pp. 699-711; Roenneberg, T., Chua, E.J., Bernardo, R., Mendoza, E., Modelling biological rhythms (2008) Curr. Biol., 18, pp. R826-R835; Schmal, C., Herzog, E.D., Herzel, H., Measuring relative coupling strength in circadian systems (2018) J. Biol. Rhythms, 33 (1), pp. 84-98; Glass, L., Mackey, M.C., (1988) From Clocks to Chaos: The Rhythms of Life, , Princeton University Press, Princeton, NJ; Abraham, U., Coupling governs entrainment range of circadian clocks (2010) Mol. Syst. Biol., 6, p. 438; Ashwin, P., Coombes, S., Nicks, R., Mathematical frameworks for oscillatory network dynamics in neuroscience (2016) J. Math. Neurosci., 6, p. 2; Schmal, C., Myung, J., Herzel, H., Bordyugov, G., Moran's i quantifies spatiotemporal pattern formation in neural imaging data (2017) Bioinformatics, 33, pp. 3072-3079; Granada, A.E., Bordyugov, G., Kramer, A., Herzel, H., Human chronotypes from a theoretical perspective (2013) PLoS ONE, 8, p. e59464; Pan, F., Mills, S.L., Massey, S.C., Screening of gap junction antagonists on dye coupling in the rabbit retina (2007) Vis. Neurosci., 24, pp. 609-618; Ono, D., Honma, S., Honma, K., Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus (2013) Nat. Commun., 4, p. 1666; Balsalobre, A., Resetting of circadian time in peripheral tissues by glucocorticoid signaling (2000) Science, 289, pp. 2344-2347; Maywood, E.S., Chesham, J.E., O'Brien, J.A., Hastings, M.H., A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits (2011) Proc. Natl Acad. Sci. USA, 108, pp. 14306-14311; Myung, J., Period coding of Bmal1 oscillators in the suprachiasmatic nucleus (2012) J. Neurosci., 32, pp. 8900-8918; Hofstetter, J.R., Mayeda, A.R., Possidente, B., Nurnberger, J.I., Jr., Quantitative trait loci (QTL) for circadian rhythms of locomotor activity in mice (1995) Behav. Genet., 25, pp. 545-556; Ono, D., Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus in parallel with behavioral outputs (2017) Proc. Natl Acad. Sci. USA, 114, pp. E3699-E3708; Zhang, Y., A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cells (2007) Am. J. Respir. Cell Mol. Biol., 36, pp. 515-519; Hara, M., Robust circadian clock oscillation and osmotic rhythms in inner medulla reflecting cortico-medullary osmotic gradient rhythm in rodent kidney (2017) Sci. Rep., 7, p. 7306; Lun, M.P., Monuki, E.S., Lehtinen, M.K., Development and functions of the choroid plexus-cerebrospinal fluid system (2015) Nat. Rev. Neurosci., 16, pp. 445-457; Vansteensel, M.J., Dissociation between circadian Per1 and neuronal and behavioral rhythms following a shifted environmental cycle (2003) Curr. Biol., 13, pp. 1538-1542; Kiessling, S., Eichele, G., Oster, H., Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag (2010) J. Clin. Invest., 120, pp. 2600-2609; Tso, C.F., Astrocytes regulate daily rhythms in the suprachiasmatic nucleus and behavior (2017) Curr. Biol., 27, pp. 1055-1061; Brancaccio, M., Patton, A.P., Chesham, J.E., Maywood, E.S., Hastings, M.H., Astrocytes control circadian timekeeping in the suprachiasmatic nucleus via glutamatergic signaling (2017) Neuron, 93, pp. 1420e1425-1435e1425; Barca-Mayo, O., Astrocyte deletion of Bmal1 alters daily locomotor activity and cognitive functions via GABA signalling (2017) Nat. Commun., 8, p. 14336; Bernard, S., Gonze, D., Cajavec, B., Herzel, H., Kramer, A., Synchronizationinduced rhythmicity of circadian oscillators in the suprachiasmatic nucleus (2007) PLoS. Comput. Biol., 3, p. e68; Gomez-Gardenes, J., Gomez, S., Arenas, A., Moreno, Y., Explosive synchronization transitions in scale-free networks (2011) Phys. Rev. Lett., 106, p. 128701; Zhang, X., Hu, X., Kurths, J., Liu, Z., Explosive synchronization in a general complex network (2013) Phys. Rev. e Stat. Nonlin. Soft Matter Phys., 88, p. 010802; Meeker, K., Wavelet measurement suggests cause of period instability in mammalian circadian neurons (2011) J. Biol. Rhythms, 26, pp. 353-362; Jovanova-Nesic, K., Choroid plexus connexin 43 expression and gap junction flexibility are associated with clinical features of acute EAE (2009) Ann. N. Y. Acad. Sci., 1173, pp. 75-82; Negoro, H., Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm (2012) Nat. Commun., 3, p. 809; Haas, J.S., Zavala, B., Landisman, C.E., Activity-dependent long-term depression of electrical synapses (2011) Science, 334, pp. 389-393; De Bock, M., A new angle on blood-CNS interfaces: A role for connexins? (2014) FEBS Lett., 588, pp. 1259-1270; Hughes, A.T., Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC2-signaling deficient mice (2015) Sci. Rep., 5, p. 14044; St John, P.C., Doyle, F.J., Quantifying stochastic noise in cultured circadian reporter cells (2015) PLoS. Comput. Biol., 11, p. e1004451; Leise, T.L., Harrington, M.E., Wavelet-based time series analysis of circadian rhythms (2011) J. Biol. Rhythms, 26, pp. 454-463; Winfree, A.T., (2001) The Geometry of Biological Time, 2. , Springer, New York, NY; Schmal, C., Myung, J., Herzel, H., Bordyugov, G., A theoretical study on seasonality (2015) Front. Neurol., 6, p. 94

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85044173112&partnerID=8YFLogxK

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U2 - 10.1038/s41467-018-03507-2

DO - 10.1038/s41467-018-03507-2

M3 - Article

VL - 9

SP - 1062

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1062

ER -