Buijink M Renate, Almog Assaf, Wit Charlotte B, Roethler Ori, Olde Engberink Anneke H O, Meijer Johanna H, Garlaschelli Diego, Rohling Jos H T, Michel Stephan
Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
Lorentz Institute for Theoretical Physics, Leiden University, Leiden, The Netherlands.
PLoS One. 2016 Dec 22;11(12):e0168954. doi: 10.1371/journal.pone.0168954. eCollection 2016.
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.
对于生活在温带地区的动物而言，日照长度的季节性变化是其生理和行为适应环境条件改变的重要线索。视交叉上核（SCN）是哺乳动物的中枢昼夜节律时钟，但在适应不同光周期方面可能也起着重要作用。SCN接收来自视网膜的直接光输入，并能够通过使电活动节律的波形接近日照时长来编码日照长度。改变整体波形需要SCN内神经元网络的重组以及神经元之间同步程度的改变；然而，其潜在机制尚不清楚。在本研究中，我们使用培养的SCN切片中的PER2::LUC生物发光成像来表征单细胞水平的网络动态，并旨在为耦合强度调制在光周期诱导的相位分散中的作用提供证据。与短光周期相比，暴露于长光周期（LP）会导致前SCN中单细胞PER2::LUC节律的峰值时间分布更广。有趣的是，LP条件下前SCN中PER2::LUC节律的单细胞周期的逐周期变异性也更高，并且与峰值时间分散呈正相关。对PER2::LUC节律的时间序列数据应用一种新的、公正的群落检测方法，揭示了具有特定空间分布的两类细胞，我们将其定义为背外侧和腹内侧SCN。对这些细胞簇的节律特征进行的事后分析表明，与前SCN中的腹内侧细胞簇相比，背外侧细胞簇的单细胞周期逐周期变异性更大。我们得出结论，SCN网络内耦合强度的变化是对观察到的单细胞周期变异性变化的合理解释，这可能导致光周期诱导的相位分布。
