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Abstract

This article describes a behaviorally, physiologically, and anatomically predictive model of how circadian rhythms are generated by each suprachiasmatic nucleus (SCN) of the mammalian hypothalamus. This gated pacemaker model is defined in terms of competing on-cell off-cell populations whose positive feedback signals are gated by slowly accumulating chemical transmitter substances. These components have also been used to model other hypothalamic circuits, notably the eating circuit. A parametric analysis of the types of oscillations supported by the model is presented. The complementary reactions to light of diurnal and nocturnal mammals as well as their similar phase response curves are obtained. The ldquodead zonerdquo of the phase response curve during the subjective day of a noctural rodent is also explained. Oscillations are suppressed by high intensities of steady light. Operations that alter the parameters of the model transmitters can phase shift or otherwise change its circadian oscillation. Effects of ablation and hormones on model oscillations are summarized. Observed oscillations include regular periodic solutions, periodic plateau solutions, rippled plateau solutions, period doubling solutions, slow modulation of oscillations over a period of months, and repeating sequences of oscillation clusters. The model period increases inversely with the transmitter accumulation rate but is insensitive to other parameter choices except near the breakdown of oscillations. The model's clocklike nature is thus a mathematical property rather than a formal postulate. A singular perturbation approach to the model's analysis is described.
Supported in part by the Air Force Office of Scientific Research (AFOSR 82-0148), the National Science Foundation (NSF MCS-82-07778), the Northeastern University Research and Scholarship Development Fund, and the Office of Naval Research (ONR-N00014-83-K0337)
Supported in part by the Air Force Office of Scientific Research (AFOSR 82-0148), the National Science Foundation (NSF IST-80-00257), and the Office of Naval Research (ONR-N00014-83-K0337)

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