New Research In
Physical Sciences
Social Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
- Agricultural Sciences
- Anthropology
- Applied Biological Sciences
- Biochemistry
- Biophysics and Computational Biology
- Cell Biology
- Developmental Biology
- Ecology
- Environmental Sciences
- Evolution
- Genetics
- Immunology and Inflammation
- Medical Sciences
- Microbiology
- Neuroscience
- Pharmacology
- Physiology
- Plant Biology
- Population Biology
- Psychological and Cognitive Sciences
- Sustainability Science
- Systems Biology
Functional network inference of the suprachiasmatic nucleus
Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved March 7, 2016 (received for review November 3, 2015)

Significance
In mammals, circadian rhythms are controlled by a network of neurons in the brain. The structure of this network dictates organism-wide behavior and adaptation to the environment. We used a neurotoxin to desynchronize this circadian network and then used tools from information theory to determine which cells communicate to establish synchronization. Our results show that this functional network consists of two densely-connected cores, surrounded by sparsely connected shell regions. These findings represent the first time, to our knowledge, that this network has been examined at single cell resolution and show that the importance of these core network regions is independent of light input.
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.
Footnotes
↵1J.H.A. and K.M. contributed equally to this work.
- ↵2To whom correspondence should be addressed. Email: petzold{at}engineering.ucsb.edu.
Author contributions: J.H.A., K.M., D.G.-F., P.C.S.J., T.J.W., F.J.D., E.D.H., and L.R.P. designed research; J.H.A., K.M., D.G.-F., P.C.S.J., T.J.W., B.B.B., and E.D.H. performed research; J.H.A., K.M., D.G.-F., P.C.S.J., B.B.B., F.J.D., E.D.H., and L.R.P. analyzed data; and J.H.A., B.B.B., and E.D.H. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1521178113/-/DCSupplemental.
Citation Manager Formats
Sign up for Article Alerts
Jump to section
You May Also be Interested in
More Articles of This Classification
Biological Sciences
Related Content
Cited by...
- Inferring dynamic topology for decoding spatiotemporal structures in complex heterogeneous networks
- Macroscopic models for networks of coupled biological oscillators
- Ontogeny of Circadian Rhythms and Synchrony in the Suprachiasmatic Nucleus
- Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms