Laboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
J Biol Rhythms. 2014 Feb;29(1):16-27. doi: 10.1177/0748730413516752.
In mammals, the central clock in the suprachiasmatic nucleus (SCN) controls physiological and behavioral circadian rhythms and is entrained to the external light-dark cycle. The ability of the SCN to entrain can be measured by exposing the animal to a light-dark cycle with a duration that deviates from 24 h (T-cycles); a wider entrainment range reflects a higher ability to entrain. The neurons of the SCN are either light responsive or light unresponsive and are mutually synchronized. The coupling and synchronization between individual SCN neurons and between groups of neurons within the SCN influence the SCN's ability to entrain. Some studies suggest that enhanced coupling decreases the entrainment range, whereas others suggest that enhanced coupling increases the entrainment range. The latter results are surprising, as they are not consistent with the prevalent assumption that the SCN is a limit cycle oscillator that has larger phase shifts when the amplitude is smaller. Here, we used the Poincaré and Goodwin models to test entrainment properties using various proportions of neurons that are responsive to an external stimulus. If all neurons receive external input, the SCN shows limit cycle behavior in all conditions. If all neurons do not receive light input, we found that the entrainment range of the SCN was positively related to coupling strength when coupling was weak. When coupling strength was stronger and above a critical value, the entrainment range was negatively correlated with coupling strength. The results obtained from our simulations were confirmed by analytical studies. Thus, the limit cycle behavior of the SCN appears to be critically dependent on the coupling strength among the neurons and the proportion of neurons that respond to the entraining stimulus.
在哺乳动物中，视交叉上核（SCN）中的中央时钟控制生理和行为的昼夜节律，并与外部的明暗周期同步。SCN 的同步能力可以通过将动物暴露在持续时间偏离 24 小时的明暗周期（T 周期）中来测量；更大的同步范围反映了更高的同步能力。SCN 的神经元要么对光有反应，要么对光没有反应，并且相互同步。单个 SCN 神经元之间以及 SCN 内神经元群体之间的耦合和同步会影响 SCN 的同步能力。一些研究表明，增强耦合会减小同步范围，而另一些研究表明，增强耦合会增加同步范围。后一种结果令人惊讶，因为它们与普遍的假设不一致，即 SCN 是一个极限环振荡器，当幅度较小时相位偏移更大。在这里，我们使用 Poincaré 和 Goodwin 模型来测试使用对外部刺激有反应的神经元的不同比例的同步特性。如果所有神经元都接收外部输入，则 SCN 在所有条件下都表现出极限环行为。如果所有神经元都没有接收光输入，我们发现当耦合强度较弱时，SCN 的同步范围与耦合强度呈正相关。当耦合强度更强且超过临界值时，同步范围与耦合强度呈负相关。我们的模拟结果得到了分析研究的证实。因此，SCN 的极限环行为似乎严重依赖于神经元之间的耦合强度以及对同步刺激有反应的神经元的比例。
