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.

Ontogeny of Circadian Rhythms and Synchrony in the Suprachiasmatic Nucleus

“…It will be intriguing to map the synaptic network topology that contributes to the phase relationships among SCN cells (Abel et al, 2016;Buijink et al, 2016).…”

Aging Affects the Capacity of Photoperiodic Adaptation Downstream from the Central Molecular Clock

“…16.039.001) was granted by the animal experiments committee Leiden. The homozygous PERIOD2::LUCIFERASE (PER2::LUC) mice were bred at the Leiden University Medical Center animal facility (see Buijink et al, 2016). We used young (4-8 months) and old (22-28 months) male PER2::LUC mice.…”

“…Therefore, we measured PER2::LUC expression in SCN cultured slices of old and young mice after the mice were reexposed for at least 2 weeks to either LP or SP following the DD period. We have previously shown that exposing young mice to LP (LD 16:8) causes a wider phase distribution of peak times and a higher cycle-to-cycle period variability of single-cell PER2::LUC rhythms in the anterior part of the SCN compared with SP (LD 8:16; Buijink et al, 2016). Since we see deficits in behavioral adaptation to photoperiod in old mice, and photoperiod can affect PER2 rhythm distribution, we may expect that the reduction in the capability to adapt to photoperiod is also seen at the molecular level.…”

From clock to functional pacemaker

“…The electrical activity patterns of single SCN neurons are less affected by photoperiod (VanderLeest et al., ) and the single‐cell waveform changes reported are not sufficient to explain adaptation of the ensemble output to day‐length (Brown & Piggins, ). Similarly studies of clock gene expression show a change in the distribution of peak expression in response to different photoperiods (Buijink et al., ; Naito, Watanabe, Tei, Yoshimura, & Ebihara, ), but also reveal spatial differences between dorsal and ventral (Evans, Leise, Castanon‐Cervantes, & Davidson, ), and between caudal and rostral SCN (Hazlerigg, Ebling, & Johnston, ; Inagaki, Honma, Ono, Tanahashi, & Honma, ). Thus, while the rhythm generating properties arise in individual cells, seasonal encoding depends on the integrity and plasticity of the SCN network.…”