Hibernation and circadian rhythms: the differences and the possible interactions

Monday, June 14 at 7:45pm (PDT)
Tuesday, June 15 at 03:45am (BST)
Tuesday, June 15 11:45am (KST)

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Shingo Gibo (RIKEN, Japan) and Gen Kurosawa (RIKEN, Japan)


Organisms living in a fluctuating environment have evolved physiological systems with various time-scales. For example, hibernators such as thirteen-lined ground squirrels, Syrian hamsters, and bears drastically decrease their body temperature and keep inactive during a season with little or no food. To our knowledge, fundamental cellular and molecular mechanisms of hibernation remain to be elusive. Meanwhile, organisms, including hibernators show daily rhythms which are often robust to external perturbations. Despite the progress of molecular studies for circadian rhythms, mechanism of the circadian period stable to temperature, is largely unknown. Toward understanding hibernation and circadian rhythms, mathematical biology can play various roles, including (1) quantification of experimental data, (2) modelling and simulation of biological systems, and (3) proposing molecular mechanisms. In this mini-symposium, we invite experimental and mathematical biologists studying hibernation and circadian rhythms. Through the discussions between the speakers and audiences, we wish to consider the differences and the possible interactions between hibernation and circadian rhythms. We also wish to consider a possible new direction of collaborations between experimental and mathematical biology toward understanding the phenomena.

Elena Gracheva

(Yale School of Medicine, United States of America)
"Neurophysiological adaptations to the unique lifestyle in mammalian hibernators"
Mammalian hibernation is fascinating. During a short period of time, hibernating animals undergo dramatic adaptive changes, including a reduction in heart and respiration rate and a decrease in core body temperature from 37°C (98.6°F) to 4°C (39°F), yet they do not experience cold-induced pain, and their organs continue to function despite being cold and deprived of oxygen for 8 month out of the year! Moreover, since these animals do not eat or drink during hibernation, they must rely solely on the management and utilization of their internal resources for long-term survival. How hibernators achieve such a remarkable physiological adaptation, remains unknown. We use hibernating 13-lined Ground squirrels (an obligatory hibernator) and Syrian hamsters (a non-obligatory hibernator), to tackle fundamental biological questions from perspectives unachievable using the standard animal models alone. Specifically, we are interested in studying molecular evolution of mammalian hibernation and cellular adaptations that these animals evolve in order to survive prolonged periods of hypothermia, water deprivation and starvation. We are also trying to pinpoint the molecular and physiological basis of hibernation induction. Comparative analysis of three rodent species—such as ground squirrels, hamsters and mice (non-hibernator)—at the behavioral, cellular and molecular levels, will help us to delineate the multitude of adaptations that hibernators evolved in order to survive harsh environment and as a result came to inhabit a wide geographical range.

Tanya Leise

(Amherst College, United States of America)
"Analysis of the Circadian Rhythms of Brown Bears During Winter Dormancy"
Applications of wavelet transforms and other methods will be demonstrated in the context of activity and body temperature records of brown bears under different entrained and free-running conditions, including during winter dormancy. Wavelet-based methods can be useful in quantifying properties of circadian rhythms, including period, phase, amplitude, quality of rhythms, and coherence between simultaneously recorded rhythms. I will also highlight the quite distinct types of information provided by discrete versus continuous wavelet transforms methods. In particular, the analysis indicates that the circadian system is functional in torpid bears even when housed in constant darkness and it continues to be responsive to phase-shifting effects of light.

Hsin-tzu Wang

(The University of Tokyo, Japan)
"Cold Ca2+ signaling for temperature compensation of circadian rhythms"
Reaction rates of almost all biochemical processes change with temperature. On the other hand, oscillation speed of the circadian clock remains nearly unchanged in a physiological range of temperatures, and this feature common to the circadian clocks is termed temperature compensation. In chemical biological screening, we found that inhibitor of Na+/Ca2+ exchanger (NCX) or Ca2+/calmodulin dependent protein kinase II (CaMKII) remarkably increased Q10 value of the period length of gene expression rhythms in mammalian fibroblasts. In response to temperature decrease, NCX elevates intracellular Ca2+ and activates CaMKII. Activated CaMKII accelerates transcriptional oscillations of clock genes, so that the period of circadian clock remains stable. Moreover, Ca2+ signal is also important for high-amplitude oscillation of the circadian rhythms, and CaMKII alleviates amplitude reduction by temperature decrease to prevent loss of cellular rhythmicity at low temperature. In mouse spontaneous behavioral rhythms, disruption of CaMKII activity caused significant decrease of the rhythmicity. Therefore, we propose that cold NCX-Ca2+-CaMKII signaling is a crucial regulator of the amplitude and the period length of the temperature-compensated circadian rhythms.

Shingo Gibo

"Waveform analysis reveals the mechanisms for circadian rhythms and hibernation"
Organisms have evolved many oscillatory systems such as circadian rhythms and hibernation. The waveforms of the biological oscillations are of various shapes. This may indicate that the various waveforms contain the important information for understanding the biological systems. In this talk, by analyzing waveform pattern, we theoretically consider (i) circadian clocks and (ii) hibernation. First, we study the robustness of circadian period to temperature. The circadian clocks consist of complex biochemical networks. Although most biochemical reactions accelerate with increasing temperature, the period of circadian clocks is stable to temperature changes. This phenomenon is called as “temperature compensation,” and the mechanism has been unclear. To understand the condition of temperature compensation, we analyzed a mathematical model for circadian clocks. Then, we found that the waveforms of gene-activity rhythms should become more non-sinusoidal when reactions become faster and simultaneously, the circadian period becomes longer or remains unchanged. From this result, we predict that the waveforms should be more distorted at higher temperature in order to achieve temperature compensated period. Next, we analyzed the temporal pattern of hibernation. Under cold and short photoperiodic conditions, Syrian hamsters enter hibernation spontaneously. During hibernation, their body temperature shows fluctuation between euthermia and hypothermia with a certain period of several days. It is called 'torpor-arousal cycle'. In this study, we analyzed the time-series of body temperature during hibernation by using generalized harmonic analysis. Then, we found that the period of torpor-arousal cycle gradually changes at hundred-days scale.

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