Effect of network architecture on synchronization and entrainment properties of the circadian oscillations in the suprachiasmatic nucleus.
Effect of network architecture on synchronization and entrainment properties of the circadian oscillations in the suprachiasmatic nucleus.
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DOI：
10.1371/journal.pcbi.1002419
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发表时间：
2012
影响因子：
4.3
通讯作者：
Gonze D
中科院分区：
文献类型：
--
作者：
Hafner M;Koeppl H;Gonze D
在哺乳动物中，下丘脑的视交叉上核（SCN）构成了中枢昼夜节律起搏器。SCN接收来自视网膜的光信号并控制外周生物钟（位于皮质、松果体、肝脏、肾脏、心脏等）。昼夜节律系统的这种分层组织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回路使时钟基因的昼夜表达成为可能。虽然所有的神经元都有相同的基因型，但在分散的细胞培养中，单个细胞的振荡是高度异质的：许多细胞呈现阻尼振荡，振荡的周期因细胞而异。此外，确保细胞间耦合的神经递质，从而同步的细胞节律，SCN的两个主要区域之间的差异。在这项工作中，提出了一个解释SCN这种异构组织的数学模型，并用于研究SCN网络拓扑结构对同步和夹带属性的影响。结果表明，与随机连接和局域连接相比，无标度网络可以获得更大幅度的振荡。具有小世界特性的网络，如本研究中使用的无标度网络，可以更快地适应光/暗周期（时差）的延迟或提前。有趣的是，一定程度的细胞异质性对同步性能并不有害，反而有助于时差反应后的同步化。当耦合两个网络与不同的拓扑结构，模仿两个区域的SCN，有效的过滤脉冲状扰动的夹带模式进行观察。这些结果表明，SCN的复杂和异构的架构降低了网络的敏感性，短期夹带扰动，而在同一时间，提高其适应能力，以长期的变化。为了适应它们的循环环境，几乎所有的生物体都开发了一个内部计时器，即生物钟。在哺乳动物中，昼夜节律起搏器由大约20，000个神经元组成，称为位于下丘脑的视交叉上核（SCN）。SCN接收来自视网膜的光信号并控制外周生物钟以确保生理过程的正确定时。在每个SCN神经元中，基因调控网络使生物钟基因的昼夜节律表达成为可能，但在分散的细胞培养中，个体动态是高度异质的：许多细胞呈现阻尼振荡，振荡的周期因细胞而异。此外，确保细胞间耦合的神经递质，从而同步的细胞节律，SCN的两个主要区域之间的差异。我们在这里提出了一个数学模型，占这种异构组织的SCN和研究的影响网络拓扑结构的同步和夹带性能。我们的研究结果表明，细胞的异质性可能有助于飞行时差后的神经元化，并表明SCN的复杂结构降低了网络对短期夹带扰动的敏感性，同时提高了其对长期变化的适应能力。
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. In order to adapt to their cycling environment, virtually all living organisms have developed an internal timer, the circadian clock. In mammals, the circadian pacemaker is composed of about 20,000 neurons, called the suprachiasmatic nucleus (SCN) located in the hypothalamus. The SCN receives light signals from the retina and controls peripheral circadian clocks to ensure the proper timing of physiological processes. In each SCN neuron, a genetic regulatory network enables the circadian expression of the clock genes, but individual dynamics 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. We present here a mathematical model that accounts for this heterogeneous organization of the SCN and study the implication of the network topology on synchronization and entrainment properties. Our results show that cellular heterogeneity may help the resynchronization after jet lag and suggest that the complex 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.
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