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Modeling Circadian Rhythm Generation in the Suprachiasmatic Nucleus with Locally Coupled Self-Sustained Oscillators: Phase Shifts and Phase Response Curves

Hanspeter Kunz

Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstr, 190, CH-8057, Zürich, Switzerland

Circadian rhythm generation in the suprachiasmatic nucleus was modeled by locally coupled self-sustained oscillators. The model is composed of 10,000 oscillators, arranged in a square array. Coupling between oscillators and standard deviation of (randomly determined) intrinsic oscillator periods were varied. A stable overall rhythm emerged. The model behavior was investigated for phase shifts of a 24-h zeitgeber cycle. Prolongation of either the dark or the light phase resulted in a lengthening of the period, whereas shortening of the dark or the light phase shortened the period. The model's response to shifts in the light-dark cycle was dependent only on the extent of the shift and was insensitive to changes in parameters. Phase response curves (PRC) and amplitude response curves were determined for single and triple 5-h light pulses (1000 lux). Single pulses lead to type 1 PRCs with larger phase shifts for weak coupling. Triple pulses generally evoked type 1 PRCs with the exception of weak coupling, where a type 0 PRC was observed.

Key Words: circadian • mathematical model • multioscillator model • phase response curve • phase shift • SCN • simulations

Journal of Biological Rhythms, Vol. 14, No. 6, 460-468 (1999)
DOI: 10.1177/074873099129001028


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