title: Functional network inference of the suprachiasmatic nucleus.
abstract: 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. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara, CA 93106; Systems Biology Program, Harvard University, Cambridge, MA 02138;
authors.forename: John H
authors.initials: JH
authors.lastname: Abel
authors.affiliation: Department of Computer Science, University of California, Santa Barbara, CA 93106;
authors.forename: Kirsten
authors.initials: K
authors.lastname: Meeker
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130;
authors.forename: Daniel
authors.initials: D
authors.lastname: Granados-Fuentes
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara, CA 93106; Biosciences Center, National Renewable Energy Laboratory, Golden, CO 80401;
authors.forename: Peter C
authors.initials: PC
authors.lastname: St John
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130;
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Department of Computer Science, University of California, Santa Barbara, CA 93106;
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Bales
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara, CA 93106; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Doyle
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130;
authors.forename: Erik D
authors.initials: ED
authors.lastname: Herzog
authors.affiliation: Department of Computer Science, University of California, Santa Barbara, CA 93106; petzold@engineering.ucsb.edu.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Petzold
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000502:physiology*; D017930:Genes, Reporter; D008822:Mice, Transgenic; D009415:Nerve Net / Q000166:cytology / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism*
keywords: biological clock; circadian oscillator; mathematical model; synchronization; systems biology