A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. V. Pacemaker Structure:A Clock for All Seasons

1. This paper is an attempt to integrate in a general model the major findings reported earlier in this series on: lability and history dependence of circadian period, τ; dependence of τ and α on light intensity as described in Aschoffs Rule; the interrelationships between τ and phase response curves; and those inconsistencies between experimental facts on entrainment and theoretical predictions based on a single oscillator with fixed parameters τ and PRC, which pointed to a more complex system. 2. The qualitative model developed consists of two oscillators. The evidence that two separate oscillators are involved in circadian activity rhythms rests largely on the "splitting" phenomenon, known to occur in several species of mammals and birds. 3. The empirical regularities of "splitting" in hamsters exposed to constant illumination (LL) are described: (i) Splitting, i.e. the dissociation of a single activity band into two components which become stably coupled in circa 180° antiphase, occurs in about 50% of the animals in 100-200 lux, and has not been observed in lower light intensities. (ii) Splitting never occurred before 40 days after the transition to LL, unless the pretreatment had been LL of low intensity. In some animals the unsplit condition returned spontaneously. (iii) The attainment of antiphase is usually accompanied by a decrease in τ, and refusion of the two components by an increase in τ. These data show that both the split and the unsplit condition are metastable states, characterized by different phase relationships (ψEM) of two constituent oscillators. ψEM is history-dependent and determines τ of the coupled system. 4. Observations in Peromyscus leucopus transferred from LL to DD to LD 12 : 12 show that the two components of the bimodal activity peak (in LD) can for some time run at different frequencies (in DD), suggesting that bimodality of activity peaks and splitting are based on the same two-oscillator system. 5. The model developed assumes the existence of two oscillators or principal groups of oscillators E and M, with opposite dependence of spontaneous frequency on light intensity. The dependence of the phase relationship (ψEM) between the two on light intensity and the dependence of τ on ψEM account for all the history-dependent characteristics of circadian pacemakers, and for the interdependence of τ, PRC, and τ-lability. The model qualitatively accommodates the interdependence of τ and α summarized in Aschoffs Rule. It is noted that the major intuitive elements in the model have been found to characterize an explicit version of it in computer simulations. The relevance of the model to seasonal change in photoperiod is discussed. A pacemaker comprising two oscillators mutually interacting but coupled separately to sunrise and sunset enhances its competence to accommodate to seasonal change in the daily pattern of external conditions; and it could well be involved in the pacemaker's known ability to discriminate between daylengths in the phenomena of photoperiodic induction