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Spontaneous Synchronization of Coupled Circadian Oscillators

Didier Gonze ^* , Samuel Bernard ^*, Christian Waltermann ^*, Achim Kramer  and Hanspeter Herzel ^*

^* Institute for Theoretical Biology, Humboldt Universität zu Berlin, Berlin, Germany; Unité de Chronobiologie Théorique, Université Libre de Bruxelles, Brussels, Belgium; and Laboratory of Chronobiology, Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany

Correspondence: Address reprint requests to Hanspeter Herzel, Institute for Theoretical Biology, Invalidenstr. 43, 10115 Berlin, Germany. Tel.: 49-30-2093-9101; E-mail: h.herzel{at}biologie.hu-berlin.de.

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.

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