Laboratory of Nonlinear Systems, School of Computer and Communication Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
PLoS Comput Biol. 2012;8(3):e1002419. doi: 10.1371/journal.pcbi.1002419. Epub 2012 Mar 8.
In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker. The SCN receives light signals from the retina and controls peripheral circadian clocks (located in the cortex, the pineal gland, the liver, the kidney, the heart, etc.). This hierarchical organization of the circadian system ensures the proper timing of physiological processes. In each SCN neuron, interconnected transcriptional and translational feedback loops enable the circadian expression of the clock genes. Although all the neurons have the same genotype, the oscillations of individual cells are highly heterogeneous in dispersed cell culture: many cells present damped oscillations and the period of the oscillations varies from cell to cell. In addition, the neurotransmitters that ensure the intercellular coupling, and thereby the synchronization of the cellular rhythms, differ between the two main regions of the SCN. In this work, a mathematical model that accounts for this heterogeneous organization of the SCN is presented and used to study the implication of the SCN network topology on synchronization and entrainment properties. The results show that oscillations with larger amplitude can be obtained with scale-free networks, in contrast to random and local connections. Networks with the small-world property such as the scale-free networks used in this work can adapt faster to a delay or advance in the light/dark cycle (jet lag). Interestingly a certain level of cellular heterogeneity is not detrimental to synchronization performances, but on the contrary helps resynchronization after jet lag. When coupling two networks with different topologies that mimic the two regions of the SCN, efficient filtering of pulse-like perturbations in the entrainment pattern is observed. These results suggest that the complex and heterogeneous architecture of the SCN decreases the sensitivity of the network to short entrainment perturbations while, at the same time, improving its adaptation abilities to long term changes.
在哺乳动物中，下丘脑的视交叉上核（SCN）构成了中央生物钟。SCN 接收来自视网膜的光信号，并控制外周生物钟（位于大脑皮层、松果腺、肝脏、肾脏、心脏等）。这种生物钟系统的层次结构确保了生理过程的适当定时。在每个 SCN 神经元中，相互连接的转录和翻译反馈环使时钟基因的昼夜节律表达成为可能。尽管所有神经元都具有相同的基因型，但在分散的细胞培养中，单个细胞的振荡高度异质：许多细胞呈现阻尼振荡，并且振荡的周期从一个细胞到另一个细胞变化。此外，确保细胞间耦合的神经递质，从而确保细胞节律的同步，在 SCN 的两个主要区域之间存在差异。在这项工作中，提出了一个考虑到 SCN 异质组织的数学模型，并用于研究 SCN 网络拓扑结构对同步和驯化特性的影响。结果表明，与随机和局部连接相比，具有无标度网络的更大幅度的振荡可以获得。在这项工作中使用的具有小世界特性的无标度网络可以更快地适应光/暗周期（时差）的延迟或提前。有趣的是，一定水平的细胞异质性不会对同步性能产生不利影响，但相反有助于时差后重新同步。当耦合两个模拟 SCN 两个区域的具有不同拓扑结构的网络时，在驯化模式中观察到对脉冲状扰动的有效滤波。这些结果表明，SCN 的复杂和异质结构降低了网络对短期驯化扰动的敏感性，同时提高了其对长期变化的适应能力。
