Gu Chang Gui, Wang Ping, Weng Tong Feng, Yang Hui Jie, Rohling Jos
Business School, University of Shanghai for Science and Technology, Shanghai 200093, P.R. China.
Department of Cell and Chemical Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
Math Biosci Eng. 2019 Mar 7;16(4):1893-1913. doi: 10.3934/mbe.2019092.
Circadian rhythms have been observed in behavioral and physiological activities of living things exposed to the natural 24 h light-darkness cycle. Interestingly, even under constant darkness, living organisms maintain a robust endogenous circadian rhythm suggesting the existence of an endogenous clock. In mammals, the endogenous clock is located in the suprachiasmatic nucleus (SCN) which is composed of about 20,000 neuronal oscillators. These neuronal oscillators are heterogeneous in their properties, including the intrinsic period, intrinsic amplitude, light information sensitivity, cellular coupling strength, intrinsic amplitudes and the topological links. In this review, we introduce the influence of the heterogeneity of these properties on the two main functions of the SCN, i.e. the free running rhythm in constant darkness and entrainment to the external cycle, based on mathematical models where heterogeneous neuronal oscillators are coupled to form a network. Our findings show that the heterogeneities can alter the free running periods under constant darkness and the entrainment ability to the external cycle for the SCN by controlling a fine balance between flexibility and robustness of the clock. These findings can explain experimental observation, e.g., why the free running periods and entrainment abilities are different between species, and shed light on the heterogeneity of the SCN network.
在暴露于自然24小时明暗循环的生物的行为和生理活动中,已观察到昼夜节律。有趣的是,即使在持续黑暗的条件下,生物体仍能维持强大的内源性昼夜节律,这表明存在一个内源性时钟。在哺乳动物中,内源性时钟位于视交叉上核(SCN),它由大约20,000个神经元振荡器组成。这些神经元振荡器在其特性上是异质的,包括固有周期、固有振幅、光信息敏感性、细胞耦合强度、固有振幅和拓扑连接。在这篇综述中,我们基于异质神经元振荡器耦合形成网络的数学模型,介绍这些特性的异质性对视交叉上核的两个主要功能的影响,即在持续黑暗中的自由运行节律以及与外部周期的同步。我们的研究结果表明,异质性可以通过控制时钟灵活性和稳健性之间的精细平衡,改变持续黑暗条件下的自由运行周期以及视交叉上核对外部周期的同步能力。这些发现可以解释实验观察结果,例如为什么不同物种之间的自由运行周期和同步能力不同,并揭示视交叉上核网络的异质性。