title: Network Dynamics Mediate Circadian Clock Plasticity.
abstract: A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian "master clock," which is DNA methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole. Interruption of neural communication by inhibiting neuronal firing or by physical cutting suppresses both SCN reorganization and period changes. Mathematical modeling suggests, and experiments confirm, that this SCN reorganization depends upon GABAergic signaling. Our results therefore show that basic circadian clock properties are governed by dynamic interactions among SCN neurons, with neuroadaptations in network function driven by the environment.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Abdelhalim
authors.initials: A
authors.lastname: Azzi
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences, Marquette University, 1250 W. Wisconsin Ave., Milwaukee, WI 53233, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Evans
authors.affiliation: Department of Mathematics and Statistics, Amherst College, 220 S. Pleasant St., Amherst, MA 01002, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Leise
authors.affiliation: RIKEN Brain Science Institute (BSI), 2-1 Hirosawa Wako City, Saitama 351-0198, Japan.
authors.forename: Jihwan
authors.initials: J
authors.lastname: Myung
authors.affiliation: RIKEN Brain Science Institute (BSI), 2-1 Hirosawa Wako City, Saitama 351-0198, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takumi
authors.affiliation: Department of Neurobiology, Morehouse School of Medicine, 720 Westview Dr., Atlanta, GA 30310, USA.
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Davidson
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Brown
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D057906:Circadian Clocks / Q000235:genetics* / Q000502:physiology; D002940:Circadian Rhythm; D019175:DNA Methylation / Q000235:genetics*; D008027:Light; D008297:Male; D051379:Mice; D008962:Models, Theoretical; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D056950:Period Circadian Proteins / Q000235:genetics; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013788:Thalamus / Q000166:cytology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D005680:gamma-Aminobutyric Acid
keywords: automation; autopatcher; in vivo; patch clamp; subcortical; thalamus; whole-cell