Chronotype and stability of spontaneous locomotor activity rhythm in BMAL1-deficient mice

Abstract

Behavior, physiological functions and cognitive performance change over the time of the day. These daily rhythms are either externally driven by rhythmic environmental cues such as the light/dark cycle (masking) or controlled by an internal circadian clock, the suprachiasmatic nucleus (SCN), which can be entrained to the light/dark cycle. Within a given species, there is genetically determined variability in the temporal preference for the onset of the active phase, the chronotype. The chronotype is the phase of entrainment between external and internal time and is largely regulated by the circadian clock. Genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population. However, little is known about the determination of the chronotype, the stability of the locomotor rhythm and the re-synchronization capacity to jet lag in an animal without a functional endogenous clock. Therefore, we analyzed the chronotype of BMAL1-deficient mice (BMAL1−/−) as well as the effects of repeated experimental jet lag on locomotor activity rhythms. Moreover, light-induced period expression in the retina was analyzed to assess the responsiveness of the circadian light input system. In contrast to wild-type mice, BMAL1−/− showed a significantly later chronotype, adapted more rapidly to both phase advance and delay but showed reduced robustness of rhythmic locomotor activity after repeated phase shifts. However, photic induction of Period in the retina was not different between the two genotypes. Our findings suggest that a disturbed clockwork is associated with a late chronotype, reduced rhythm stability and higher vulnerability to repeated external desynchronization.

• Bmal1
• clock genes
• jet lag
• light
• masking
• per1
• per2

Acknowledgements

The authors thank R. Fassbender for technical assistance and C. Bradfield for providing BMAL−/− mice.

Declaration of interest

H.W.K. has received honoraria for lectures from Servier. M.P. and C.v.G. report no known conflicts of interest. This work was supported by the Dr. Senckenbergische Stiftung (H.-W.K.). The authors alone are responsible for the content and writing of the article.