Functional network inference of the suprachiasmatic nucleus

Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel; St. John, Peter C.; Wang, Thomas J.; Bales, Benjamin B.; Doyle, III, Francis J.; Herzog, Erik D.; Petzold, Linda R.

doi:10.1073/pnas.1521178113

Functional network inference of the suprachiasmatic nucleus

Journal Article · Mon Apr 04 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1521178113· OSTI ID:1249409

Abel, John H. ^[1]; Meeker, Kirsten ^[2]; Granados-Fuentes, Daniel ^[3]; St. John, Peter C. ^[4]; Wang, Thomas J. ^[3]; Bales, Benjamin B. ^[2]; Doyle, III, Francis J. ^[1]; Herzog, Erik D. ^[3]; Petzold, Linda R. ^[2]

Univ. of California, Santa Barbara, CA (United States); Harvard Univ., Cambridge, MA (United States)
Univ. of California, Santa Barbara, CA (United States)
Washington Univ., St. Louis, MO (United States)
Univ. of California, Santa Barbara, CA (United States); National Renewable Energy Lab. (NREL), Golden, CO (United States)

In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Lastly, we used two computational models of circadian neurons to validate our predictions of network structure.

View Accepted Manuscript (DOE)

Research Organization:: National Renewable Energy Laboratory (NREL), Golden, CO (United States)

Sponsoring Organization:: National Institutes of Health; U.S. Army Research Office

Grant/Contract Number:: AC36-08GO28308

OSTI ID:: 1249409

Report Number(s):: NREL/JA--2700-66276

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 16 Vol. 113; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (63)

Evaluating causal relations in neural systems: Granger causality, directed transfer function and statistical assessment of significance Kamiński, Maciej; Ding, Mingzhou; Truccolo, Wilson A. Biological Cybernetics, Vol. 85, Issue 2 https://doi.org/10.1007/s004220000235	journal	August 2001
The circadian rhythm of body temperature Refinetti, Roberto; Menaker, Michael Physiology & Behavior, Vol. 51, Issue 3 https://doi.org/10.1016/0031-9384(92)90188-8	journal	March 1992
Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms Welsh, David K.; Logothetis, Diomedes E.; Meister, Markus Neuron, Vol. 14, Issue 4 https://doi.org/10.1016/0896-6273(95)90214-7	journal	April 1995
Cellular Construction of a Circadian Clock: Period Determination in the Suprachiasmatic Nuclei Liu, Chen; Weaver, David R.; Strogatz, Steven H. Cell, Vol. 91, Issue 6 https://doi.org/10.1016/S0092-8674(00)80473-0	journal	December 1997
The role of glutamate in the photic regulation of the suprachiasmatic nucleus Ebling, F. Progress in Neurobiology, Vol. 50, Issue 2-3 https://doi.org/10.1016/S0301-0082(96)00032-9	journal	October 1996
Multicellular Model for Intercellular Synchronization in Circadian Neural Networks Vasalou, Christina; Herzog, Erik D.; Henson, Michael A. Biophysical Journal, Vol. 101, Issue 1 https://doi.org/10.1016/j.bpj.2011.04.051	journal	July 2011
Amplitude Metrics for Cellular Circadian Bioluminescence Reporters St. John, Peter C.; Taylor, Stephanie R.; Abel, John H. Biophysical Journal, Vol. 107, Issue 11 https://doi.org/10.1016/j.bpj.2014.10.026	journal	December 2014
Circadian Gene Expression in Individual Fibroblasts Nagoshi, Emi; Saini, Camille; Bauer, Christoph Cell, Vol. 119, Issue 5 https://doi.org/10.1016/j.cell.2004.11.015	journal	November 2004
Intercellular Coupling Confers Robustness against Mutations in the SCN Circadian Clock Network Liu, Andrew C.; Welsh, David K.; Ko, Caroline H. Cell, Vol. 129, Issue 3 https://doi.org/10.1016/j.cell.2007.02.047	journal	May 2007
A GABAergic Mechanism Is Necessary for Coupling Dissociable Ventral and Dorsal Regional Oscillators within the Circadian Clock Albus, Henk; Vansteensel, Mariska J.; Michel, Stephan Current Biology, Vol. 15, Issue 10 https://doi.org/10.1016/j.cub.2005.03.051	journal	May 2005
GABA Networks Destabilize Genetic Oscillations in the Circadian Pacemaker Freeman, G. Mark; Krock, Rebecca M.; Aton, Sara J. Neuron, Vol. 78, Issue 5 https://doi.org/10.1016/j.neuron.2013.04.003	journal	June 2013
Dynamic Interactions Mediated by Nonredundant Signaling Mechanisms Couple Circadian Clock Neurons Evans, Jennifer A.; Leise, Tanya L.; Castanon-Cervantes, Oscar Neuron, Vol. 80, Issue 4 https://doi.org/10.1016/j.neuron.2013.08.022	journal	November 2013
Collective dynamics of ‘small-world’ networks Watts, Duncan J.; Strogatz, Steven H. Nature, Vol. 393, Issue 6684 https://doi.org/10.1038/30918	journal	June 1998
Molecular clocks: mastering time by gene regulation Sassone-Corsi, Paolo Nature, Vol. 392, Issue 6679 https://doi.org/10.1038/31821	journal	April 1998
Dynamical signatures of cellular fluctuations and oscillator stability in peripheral circadian clocks Rougemont, Jacques; Naef, Felix Molecular Systems Biology, Vol. 3, Issue 1 https://doi.org/10.1038/msb4100130	journal	January 2007
Constant light desynchronizes mammalian clock neurons Ohta, Hidenobu; Yamazaki, Shin; McMahon, Douglas G. Nature Neuroscience, Vol. 8, Issue 3 https://doi.org/10.1038/nn1395	journal	January 2005
Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons Aton, Sara J.; Colwell, Christopher S.; Harmar, Anthony J. Nature Neuroscience, Vol. 8, Issue 4 https://doi.org/10.1038/nn1419	journal	March 2005
Spatially embedded growing small-world networks Zitin, Ari; Gorowara, Alexander; Squires, Shane Scientific Reports, Vol. 4, Issue 1 https://doi.org/10.1038/srep07047	journal	November 2014
Circadian rhythms and molecular noise Gonze, Didier; Goldbeter, Albert Chaos: An Interdisciplinary Journal of Nonlinear Science, Vol. 16, Issue 2 https://doi.org/10.1063/1.2211767	journal	June 2006
Physiological significance of a peripheral tissue circadian clock Lamia, K. A.; Storch, K. -F.; Weitz, C. J. Proceedings of the National Academy of Sciences, Vol. 105, Issue 39 https://doi.org/10.1073/pnas.0806717105	journal	September 2008
Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons Webb, A. B.; Angelo, N.; Huettner, J. E. Proceedings of the National Academy of Sciences, Vol. 106, Issue 38 https://doi.org/10.1073/pnas.0902768106	journal	September 2009
A neuropeptide speeds circadian entrainment by reducing intercellular synchrony An, S.; Harang, R.; Meeker, K. Proceedings of the National Academy of Sciences, Vol. 110, Issue 46 https://doi.org/10.1073/pnas.1307088110	journal	October 2013
Distinct roles for GABA across multiple timescales in mammalian circadian timekeeping DeWoskin, Daniel; Myung, Jihwan; Belle, Mino D. C. Proceedings of the National Academy of Sciences, Vol. 112, Issue 29 https://doi.org/10.1073/pnas.1420753112	journal	June 2015
GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time Myung, Jihwan; Hong, Sungho; DeWoskin, Daniel Proceedings of the National Academy of Sciences, Vol. 112, Issue 29 https://doi.org/10.1073/pnas.1421200112	journal	June 2015
The suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker. Schwartz, W. J.; Gross, R. A.; Morton, M. T. Proceedings of the National Academy of Sciences, Vol. 84, Issue 6 https://doi.org/10.1073/pnas.84.6.1694	journal	March 1987
StochKit2: software for discrete stochastic simulation of biochemical systems with events Sanft, K. R.; Wu, S.; Roh, M. Bioinformatics, Vol. 27, Issue 17 https://doi.org/10.1093/bioinformatics/btr401	journal	July 2011
minerva and minepy: a C engine for the MINE suite and its R, Python and MATLAB wrappers Albanese, Davide; Filosi, Michele; Visintainer, Roberto Bioinformatics, Vol. 29, Issue 3 https://doi.org/10.1093/bioinformatics/bts707	journal	December 2012
It is not the parts, but how they interact that determines the behaviour of circadian rhythms across scales and organisms DeWoskin, Daniel; Geng, Weihua; Stinchcombe, Adam R. Interface Focus, Vol. 4, Issue 3 https://doi.org/10.1098/rsfs.2013.0076	journal	June 2014
Design principles for phase-splitting behaviour of coupled cellular oscillators: clues from hamsters with ‘split’ circadian rhythms Indic, Premananda; Schwartz, William J.; Paydarfar, David Journal of The Royal Society Interface, Vol. 5, Issue 25 https://doi.org/10.1098/rsif.2007.1248	journal	December 2007
Growing networks with geographical attachment preference: Emergence of small worlds Ozik, Jonathan; Hunt, Brian R.; Ott, Edward Physical Review E, Vol. 69, Issue 2 https://doi.org/10.1103/PhysRevE.69.026108	journal	February 2004
Functional structure of cortical neuronal networks grown in vitro Bettencourt, Luís M. A.; Stephens, Greg J.; Ham, Michael I. Physical Review E, Vol. 75, Issue 2 https://doi.org/10.1103/PhysRevE.75.021915	journal	February 2007
Mean-Field Solution of the Small-World Network Model Newman, M. E. J.; Moore, C.; Watts, D. J. Physical Review Letters, Vol. 84, Issue 14 https://doi.org/10.1103/PhysRevLett.84.3201	journal	April 2000
Scale-Free Brain Functional Networks Eguíluz, Victor M.; Chialvo, Dante R.; Cecchi, Guillermo A. Physical Review Letters, Vol. 94, Issue 1 https://doi.org/10.1103/PhysRevLett.94.018102	journal	January 2005
Statistical mechanics of complex networks Albert, Réka; Barabási, Albert-László Reviews of Modern Physics, Vol. 74, Issue 1 https://doi.org/10.1103/RevModPhys.74.47	journal	January 2002
A Coupled Stochastic Model Explains Differences in Cry Knockout Behavior Abel, John H.; Widmer, Lukas A.; John, Peter C. St. IEEE Life Sciences Letters, Vol. 1, Issue 1 https://doi.org/10.1109/LLS.2015.2439498	journal	June 2015
Mechanism of bilateral communication in the suprachiasmatic nucleus Michel, Stephan; Marek, Roger; vanderLeest, Henk T. European Journal of Neuroscience, Vol. 37, Issue 6 https://doi.org/10.1111/ejn.12109	journal	January 2013
Daily and seasonal adaptation of the circadian clock requires plasticity of the SCN neuronal network: Plasticity of the SCN neuronal network Meijer, Johanna H.; Michel, Stephan; VanderLeest, Henk T. European Journal of Neuroscience, Vol. 32, Issue 12 https://doi.org/10.1111/j.1460-9568.2010.07522.x	journal	December 2010
Synchronization of Cellular Clocks in the Suprachiasmatic Nucleus Yamaguchi, Shun; Isejima, Hiromi; Matsuo, Takuya Science, Vol. 302, Issue 5649 https://doi.org/10.1126/science.1089287	journal	November 2003
Circadian Integration of Metabolism and Energetics Bass, J.; Takahashi, J. S. Science, Vol. 330, Issue 6009 https://doi.org/10.1126/science.1195027	journal	December 2010
Temperature as a Universal Resetting Cue for Mammalian Circadian Oscillators Buhr, E. D.; Yoo, S. -H.; Takahashi, J. S. Science, Vol. 330, Issue 6002 https://doi.org/10.1126/science.1195262	journal	October 2010
Detecting Novel Associations in Large Data Sets Reshef, D. N.; Reshef, Y. A.; Finucane, H. K. Science, Vol. 334, Issue 6062 https://doi.org/10.1126/science.1205438	journal	December 2011
Antiphase Oscillation of the Left and Right Suprachiasmatic Nuclei de la, H. O. Science, Vol. 290, Issue 5492 https://doi.org/10.1126/science.290.5492.799	journal	October 2000
Decoupling of Receptor and Downstream Signals in the Akt Pathway by Its Low-Pass Filter Characteristics Fujita, K. A.; Toyoshima, Y.; Uda, S. Science Signaling, Vol. 3, Issue 132 https://doi.org/10.1126/scisignal.2000810	journal	July 2010
Power-Law Distributions in Empirical Data Clauset, Aaron; Shalizi, Cosma Rohilla; Newman, M. E. J. SIAM Review, Vol. 51, Issue 4 https://doi.org/10.1137/070710111	journal	November 2009
Suprachiasmatic Nucleus: Cell Autonomy and Network Properties Welsh, David K.; Takahashi, Joseph S.; Kay, Steve A. Annual Review of Physiology, Vol. 72, Issue 1 https://doi.org/10.1146/annurev-physiol-021909-135919	journal	March 2010
Temporal Precision in the Mammalian Circadian System: A Reliable Clock from Less Reliable Neurons Herzog, Erik D.; Aton, Sara J.; Numano, Rika Journal of Biological Rhythms, Vol. 19, Issue 1 https://doi.org/10.1177/0748730403260776	journal	February 2004
Bimodal Clock Gene Expression in Mouse Suprachiasmatic Nucleus and Peripheral Tissues Under a 7-Hour Light and 5-Hour Dark Schedule Watanabe, Tsuyoshi; Naito, Emiko; Nakao, Nobuhiro Journal of Biological Rhythms, Vol. 22, Issue 1 https://doi.org/10.1177/0748730406295435	journal	February 2007
Small-World Network Models of Intercellular Coupling Predict Enhanced Synchronization in the Suprachiasmatic Nucleus Vasalou, Christina; Herzog, Erik D.; Henson, Michael A. Journal of Biological Rhythms, Vol. 24, Issue 3 https://doi.org/10.1177/0748730409333220	journal	May 2009
Transcription-Based Oscillator Model for Light-Induced Splitting as Antiphase Circadian Gene Expression in the Suprachiasmatic Nuclei Schroder, Sondra; Herzog, Erik D.; Kiss, István Z. Journal of Biological Rhythms, Vol. 27, Issue 1 https://doi.org/10.1177/0748730411429659	journal	February 2012
Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body Evans, Jennifer A.; Suen, Ting-Chung; Callif, Ben L. BMC Biology, Vol. 13, Issue 1 https://doi.org/10.1186/s12915-015-0157-x	journal	June 2015
System-Driven and Oscillator-Dependent Circadian Transcription in Mice with a Conditionally Active Liver Clock Kornmann, Benoît; Schaad, Olivier; Bujard, Hermann PLoS Biology, Vol. 5, Issue 2 https://doi.org/10.1371/journal.pbio.0050034	journal	January 2007
Emergence of Noise-Induced Oscillations in the Central Circadian Pacemaker Ko, Caroline H.; Yamada, Yujiro R.; Welsh, David K. PLoS Biology, Vol. 8, Issue 10 https://doi.org/10.1371/journal.pbio.1000513	journal	October 2010
Synchronization-Induced Rhythmicity of Circadian Oscillators in the Suprachiasmatic Nucleus Bernard, Samuel; Gonze, Didier; Čajavec, Branka PLoS Computational Biology, Vol. 3, Issue 4 https://doi.org/10.1371/journal.pcbi.0030068	journal	January 2007
Effect of Network Architecture on Synchronization and Entrainment Properties of the Circadian Oscillations in the Suprachiasmatic Nucleus Hafner, Marc; Koeppl, Heinz; Gonze, Didier PLoS Computational Biology, Vol. 8, Issue 3 https://doi.org/10.1371/journal.pcbi.1002419	journal	March 2012
Timing of Neuropeptide Coupling Determines Synchrony and Entrainment in the Mammalian Circadian Clock Ananthasubramaniam, Bharath; Herzog, Erik D.; Herzel, Hanspeter PLoS Computational Biology, Vol. 10, Issue 4 https://doi.org/10.1371/journal.pcbi.1003565	journal	April 2014
Quantifying Stochastic Noise in Cultured Circadian Reporter Cells St. John, Peter C.; Doyle, Francis J. PLOS Computational Biology, Vol. 11, Issue 11 https://doi.org/10.1371/journal.pcbi.1004451	journal	November 2015
Evaluation of the Performance of Information Theory-Based Methods and Cross-Correlation to Estimate the Functional Connectivity in Cortical Networks Garofalo, Matteo; Nieus, Thierry; Massobrio, Paolo PLoS ONE, Vol. 4, Issue 8 https://doi.org/10.1371/journal.pone.0006482	journal	August 2009
powerlaw: A Python Package for Analysis of Heavy-Tailed Distributions Alstott, Jeff; Bullmore, Ed; Plenz, Dietmar PLoS ONE, Vol. 9, Issue 1 https://doi.org/10.1371/journal.pone.0085777	journal	January 2014
On the Inference of Functional Circadian Networks Using Granger Causality Pourzanjani, Arya; Herzog, Erik D.; Petzold, Linda R. PLOS ONE, Vol. 10, Issue 9 https://doi.org/10.1371/journal.pone.0137540	journal	September 2015
Two Antiphase Oscillations Occur in Each Suprachiasmatic Nucleus of Behaviorally Split Hamsters Yan, L. Journal of Neuroscience, Vol. 25, Issue 39 https://doi.org/10.1523/JNEUROSCI.2538-05.2005	journal	September 2005
Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells Bieler, Jonathan; Cannavo, Rosamaria; Gustafson, Kyle Molecular Systems Biology, Vol. 10, Issue 7 https://doi.org/10.15252/msb.20145218	journal	July 2014
A Molecular Model for Intercellular Synchronization in the Mammalian Circadian Clock To, Tsz-Leung; Henson, Michael A.; Herzog, Erik D. Biophysical Journal, Vol. 92, Issue 11 https://doi.org/10.1529/biophysj.106.094086	journal	June 2007
Dim Nighttime Illumination Interacts With Parametric Effects of Bright Light to Increase the Stability of Circadian Rhythm Bifurcation in Hamsters Evans, Jennifer A.; Elliott, Jeffrey A.; Gorman, Michael R. Chronobiology International, Vol. 28, Issue 6 https://doi.org/10.3109/07420528.2011.591952	journal	July 2011

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97 MATHEMATICS AND COMPUTING
biological clock
circadian oscillator
mathematical model
synchronization
systems biology

Functional network inference of the suprachiasmatic nucleus

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