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Title: Functional network inference of the suprachiasmatic nucleus

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [3];  [4];  [3];  [2];  [1];  [3];  [2]
  1. Univ. of California, Santa Barbara, CA (United States); Harvard Univ., Cambridge, MA (United States)
  2. Univ. of California, Santa Barbara, CA (United States)
  3. Washington Univ., St. Louis, MO (United States)
  4. 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.

Research Organization:
National Renewable Energy Lab. (NREL), Golden, CO (United States)
Sponsoring Organization:
National Institutes of Health (NIH); US Army Research Office (ARO)
Grant/Contract Number:
AC36-08GO28308; 1R01GM096873-01; W911NF-09-0001
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, Vol. 113, Issue 16; Related Information: Proceedings of the National Academy of Sciences of the United States of America; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 40 works
Citation information provided by
Web of Science

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Long-range temporal coordination of gene expression in synthetic microbial consortia journal October 2019
Inferring dynamic topology for decoding spatiotemporal structures in complex heterogeneous networks journal August 2018
Moran’s I quantifies spatio-temporal pattern formation in neural imaging data journal May 2017
Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms journal January 2017
Ott-Antonsen ansatz truncation of a circular cumulant series journal December 2019
Macroscopic models for networks of coupled biological oscillators journal August 2018
Model-based Inference of a Directed Network of Circadian Neurons journal August 2018
Disassortative Network Structure Improves the Synchronization between Neurons in the Suprachiasmatic Nucleus journal July 2019
Macroscopic Models for Human Circadian Rhythms journal October 2019
Uncovering functional signature in neural systems via random matrix theory journal May 2019
Macroscopic Models for Networks of Coupled Biological Oscillators preprint January 2017