Weakly circadian cells improve resynchrony.
Weakly circadian cells improve resynchrony.
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DOI：
10.1371/journal.pcbi.1002787
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发表时间：
2012
影响因子：
4.3
通讯作者：
Herzog ED
中科院分区：
文献类型：
--
作者：
Webb AB;Taylor SR;Thoroughman KA;Doyle FJ 3rd;Herzog ED
哺乳动物的视交叉上核（SCN）含有数千个能够产生近24小时节律的神经元。当从它们的网络中分离时，SCN神经元表现出一系列振荡表型：持续或阻尼振荡，或振荡模式。这种变异性的影响尚不清楚。在实验中，我们发现SCN外植体内的细胞通过重新建立波的节律性和同步性从药理学诱导的去极化中恢复，而不依赖于其内在的昼夜节律周期。因此，我们假设细胞在网络内的位置也可能决定其去极化。为了测试这一点，我们采用了一个确定性的，机械模型的昼夜节律振荡器，我们可以独立地控制细胞的内在和网络连接参数。我们发现，关键参数的微小变化产生了生物细胞中观察到的全范围振荡表型，包括周期，振幅和循环能力的相似分布。该模型还预测，较弱的振荡器比较强的振荡器更容易调整它们的相位。使用这些模型细胞，我们探索了它们在网络中的数量和位置的潜在生物学后果。我们发现，当弱振子处于网络中的高度连接节点时，种群同步程度更高。一个数学上独立的相位振幅模型重现了这些发现。因此，细胞内参数的微小差异会导致细胞振荡能力的巨大变化，但网络中弱振荡子的位置也会严重影响种群的同步程度。昼夜节律是地球上几乎所有生物体都经历的生物过程中每天近24小时的振荡。单个细胞包含一个分子钟，它驱动生理学中的昼夜节律，当许多细胞在群体中同步时，它驱动日常行为。我们假设，细胞内在特性的微小差异允许细胞之间的昼夜节律周期和振幅的多样性。我们观察了昼夜节律细胞和它们的同步之前，期间和之后限制细胞之间的通信，然后比较它们的内在特性，他们的同步行为。我们发现，无节律的，弱振荡的，自我维持的昼夜节律细胞重新加入了独立于其细胞内在振荡的节奏人群。使用昼夜节律细胞的机械计算模型，我们发现，通过包括更多的弱振荡器或通过将弱振荡器放置在网络中更多的连接节点上，可以增强生物化。我们的结论是，内在属性（如振荡器的弱点和反应）和网络结构（如弱振荡器的位置）可以独立缓冲扰动的组织节奏。这揭示了细胞和网络特性如何对昼夜节律细胞系统施加规则，这些系统必须从非同步状态实现同步，例如在围产期发育期间或被迫克服社会对睡眠-觉醒行为的限制时，例如早班或晚班。
The mammalian suprachiasmatic nuclei (SCN) contain thousands of neurons capable of generating near 24-h rhythms. When isolated from their network, SCN neurons exhibit a range of oscillatory phenotypes: sustained or damping oscillations, or arrhythmic patterns. The implications of this variability are unknown. Experimentally, we found that cells within SCN explants recover from pharmacologically-induced desynchrony by re-establishing rhythmicity and synchrony in waves, independent of their intrinsic circadian period We therefore hypothesized that a cell's location within the network may also critically determine its resynchronization. To test this, we employed a deterministic, mechanistic model of circadian oscillators where we could independently control cell-intrinsic and network-connectivity parameters. We found that small changes in key parameters produced the full range of oscillatory phenotypes seen in biological cells, including similar distributions of period, amplitude and ability to cycle. The model also predicted that weaker oscillators could adjust their phase more readily than stronger oscillators. Using these model cells we explored potential biological consequences of their number and placement within the network. We found that the population synchronized to a higher degree when weak oscillators were at highly connected nodes within the network. A mathematically independent phase-amplitude model reproduced these findings. Thus, small differences in cell-intrinsic parameters contribute to large changes in the oscillatory ability of a cell, but the location of weak oscillators within the network also critically shapes the degree of synchronization for the population. Circadian rhythms are daily, near 24-h oscillations in biological processes that nearly all organisms on Earth experience. Single cells contain a molecular clock that drives circadian rhythms in physiology and, when many cells synchronize in a population, daily behaviors. We hypothesized that small differences in intrinsic cellular properties allow for a diversity of circadian periods and amplitudes across cells. We observed circadian cells and their synchrony before, during, and after limiting communication between cells and then compared their intrinsic properties to their resynchronization behavior. We found that arrhythmic, weakly oscillating, and self-sustained circadian cells rejoined the rhythmic population independent of their cell-intrinsic oscillations. Using a mechanistic computational model of circadian cells, we found that resynchronization could be enhanced by including more weak oscillators or by placing weak oscillators at more connected nodes in the network. We conclude that intrinsic properties (e.g. oscillator weakness and responsiveness) and network structure (e.g. positions of weak oscillators) can independently buffer tissue rhythms from perturbations. This reveals how cellular and network properties impose rules on systems of circadian cells that must achieve synchrony from a desynchronized state, for example during perinatal development or when forced to overcome societal constraints on sleep-wake behavior, such as working early or late shifts.
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