Functional Network Inference of the Suprachiasmatic Nucleus

Peter St. John, John Abel, Kirsten Meeker, Daniel Granados-Fuentes, Thomas Wang, Benjamin Bales, Francis Doyle III, Erik Herzog, Linda Petzold

Research output: Contribution to journalArticlepeer-review

58 Scopus Citations

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.
Original languageAmerican English
Pages (from-to)4512-4517
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number16
DOIs
StatePublished - 2016

NREL Publication Number

  • NREL/JA-2700-66276

Keywords

  • biological clock
  • circadian oscillator
  • mathematical model
  • synchronization
  • systems biology

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