title: Evidence for Weakened Intercellular Coupling in the Mammalian Circadian Clock under Long Photoperiod.
abstract: For animals living in temperate latitudes, seasonal changes in day length are an important cue for adaptations of their physiology and behavior to the altered environmental conditions. The suprachiasmatic nucleus (SCN) is known as the central circadian clock in mammals, but may also play an important role in adaptations to different photoperiods. The SCN receives direct light input from the retina and is able to encode day-length by approximating the waveform of the electrical activity rhythm to the duration of daylight. Changing the overall waveform requires a reorganization of the neuronal network within the SCN with a change in the degree of synchrony between the neurons; however, the underlying mechanisms are yet unknown. In the present study we used PER2::LUC bioluminescence imaging in cultured SCN slices to characterize network dynamics on the single-cell level and we aimed to provide evidence for a role of modulations in coupling strength in the photoperiodic-induced phase dispersal. Exposure to long photoperiod (LP) induced a larger distribution of peak times of the single-cell PER2::LUC rhythms in the anterior SCN, compared to short photoperiod. Interestingly, the cycle-to-cycle variability in single-cell period of PER2::LUC rhythms is also higher in the anterior SCN in LP, and is positively correlated with peak time dispersal. Applying a new, impartial community detection method on the time series data of the PER2::LUC rhythm revealed two clusters of cells with a specific spatial distribution, which we define as dorsolateral and ventromedial SCN. Post hoc analysis of rhythm characteristics of these clusters showed larger cycle-to-cycle single-cell period variability in the dorsolateral compared to the ventromedial cluster in the anterior SCN. We conclude that a change in coupling strength within the SCN network is a plausible explanation to the observed changes in single-cell period variability, which can contribute to the photoperiod-induced phase distribution.
authors.affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M Renate
authors.initials: MR
authors.lastname: Buijink
authors.affiliation: Lorentz Institute for Theoretical Physics, Leiden University, Leiden, The Netherlands.
authors.forename: Assaf
authors.initials: A
authors.lastname: Almog
authors.affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Charlotte B
authors.initials: CB
authors.lastname: Wit
authors.affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ori
authors.initials: O
authors.lastname: Roethler
authors.affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anneke H O
authors.initials: AH
authors.lastname: Olde Engberink
authors.affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johanna H
authors.initials: JH
authors.lastname: Meijer
authors.affiliation: Lorentz Institute for Theoretical Physics, Leiden University, Leiden, The Netherlands.
authors.forename: Diego
authors.initials: D
authors.lastname: Garlaschelli
authors.affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jos H T
authors.initials: JH
authors.lastname: Rohling
authors.affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stephan
authors.initials: S
authors.lastname: Michel
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002940:Circadian Rhythm; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D009415:Nerve Net; D017440:Photoperiod; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000502:physiology*