title: Spontaneous synchronization of coupled circadian oscillators.
abstract: In mammals, the circadian pacemaker, which controls daily rhythms, is located in the suprachiasmatic nucleus (SCN). Circadian oscillations are generated in individual SCN neurons by a molecular regulatory network. Cells oscillate with periods ranging from 20 to 28 h, but at the tissue level, SCN neurons display significant synchrony, suggesting a robust intercellular coupling in which neurotransmitters are assumed to play a crucial role. We present a dynamical model for the coupling of a population of circadian oscillators in the SCN. The cellular oscillator, a three-variable model, describes the core negative feedback loop of the circadian clock. The coupling mechanism is incorporated through the global level of neurotransmitter concentration. Global coupling is efficient to synchronize a population of 10,000 cells. Synchronized cells can be entrained by a 24-h light-dark cycle. Simulations of the interaction between two populations representing two regions of the SCN show that the driven population can be phase-leading. Experimentally testable predictions are: 1), phases of individual cells are governed by their intrinsic periods; and 2), efficient synchronization is achieved when the average neurotransmitter concentration would dampen individual oscillators. However, due to the global neurotransmitter oscillation, cells are effectively synchronized.
authors.affiliation: Institute for Theoretical Biology, Humboldt Universität zu Berlin, Berlin, Germany.
authors.forename: Didier
authors.initials: D
authors.lastname: Gonze
authors.forename: Samuel
authors.initials: S
authors.lastname: Bernard
authors.forename: Christian
authors.initials: C
authors.lastname: Waltermann
authors.forename: Achim
authors.initials: A
authors.lastname: Kramer
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Herzel
mesh_terms: D000818:Animals; D001683:Biological Clocks; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008027:Light; D008954:Models, Biological; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009991:Oscillometry / Q000379:methods*; D010507:Periodicity; D012333:RNA, Messenger / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D018377:Neurotransmitter Agents; D012333:RNA, Messenger