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Circadian rhythms are internal processes repeating approximately every 24 hours in living organisms. The dominant circadian pacemaker is synchronized to the environmental light-dark cycle. Other circadian pacemakers, which can have noncanonical circadian mechanisms, are revealed by arousing stimuli, such as scheduled feeding, palatable meals and running wheel access, or methamphetamine administration. Organisms also have ultradian rhythms, which have periods shorter than circadian rhythms. However, the biological mechanism, origin, and functional significance of ultradian rhythms are not well-elucidated. The dominant circadian rhythm often masks ultradian rhythms; therefore, we disabled the canonical circadian clock of mice by knocking out Per1/2/3 genes, where Per1 and Per2 are essential components of the mammalian light-sensitive circadian mechanism. Furthermore, we recorded wheel-running activity every minute under constant darkness for 272 days. We then investigated rhythmic components in the absence of external influences, applying unique multiscale time-resolved methods to analyze the oscillatory dynamics with time-varying frequencies. We found four rhythmic components with periods of ∼17 h, ∼8 h, ∼4 h, and ∼20 min. When the ∼17-h rhythm was prominent, the ∼8-h rhythm was of low amplitude. This phenomenon occurred periodically approximately every 2-3 weeks. We found that the ∼4-h and ∼20-min rhythms were harmonics of the ∼8-h rhythm. Coupling analysis of the ridge-extracted instantaneous frequencies revealed strong and stable phase coupling from the slower oscillations (∼17, ∼8, and ∼4 h) to the faster oscillations (∼20 min), and weak and less stable phase coupling in the reverse direction and between the slower oscillations. Together, this study elucidated the relationship between the oscillators in the absence of the canonical circadian clock, which is critical for understanding their functional significance. These studies are essential as disruption of circadian rhythms contributes to diseases, such as cancer and obesity, as well as mood disorders. [ABSTRACT FROM AUTHOR]

Light is the primary signal that calibrates circadian neural circuits and thus coordinates daily physiological and behavioral rhythms with solar entrainment cues. Drosophila and mammalian circadian circuits consist of diverse populations of cellular oscillators that exhibit a wide range of dynamic light responses, periods, phases, and degrees of synchrony. How heterogeneous circadian circuits can generate robust physiological rhythms while remaining flexible enough to respond to synchronizing stimuli has long remained enigmatic. Cryptochrome is a short-wavelength photoreceptor that is endogenously expressed in approximately half of Drosophila circadian neurons. In a previous study, physiological light response was measured using real-time bioluminescence recordings in Drosophila whole-brain explants, which remain intrinsically light-sensitive. Here we apply analysis of real-time bioluminescence experimental data to show detailed dynamic ensemble representations of whole circadian circuit light entrainment at single neuron resolution. Organotypic whole-brain explants were either maintained in constant darkness (DD) for 6 days or exposed to a phase-advancing light pulse on the second day. We find that stronger circadian oscillators support robust overall circuit rhythmicity in DD, whereas weaker oscillators can be pushed toward transient desynchrony and damped amplitude to facilitate a new state of phase-shifted network synchrony. Additionally, we use mathematical modeling to examine how a network composed of distinct oscillator types can give rise to complex dynamic signatures in DD conditions and in response to simulated light pulses. Simulations suggest that complementary coupling mechanisms and a combination of strong and weak oscillators may enable a robust yet flexible circadian network that promotes both synchrony and entrainment. A more complete understanding of how the properties of oscillators and their signaling mechanisms facilitate their distinct roles in light entrainment may allow us to direct and augment the circadian system to speed recovery from jet lag, shift work, and seasonal affective disorder.