Gonze Didier, Bernard Samuel, Waltermann Christian, Kramer Achim, Herzel Hanspeter
Institute for Theoretical Biology, Humboldt Universität zu Berlin, Berlin, Germany.
Biophys J. 2005 Jul;89(1):120-9. doi: 10.1529/biophysj.104.058388. Epub 2005 Apr 22.
In mammals, the circadian pacemaker, which controls daily rhythms, is located in the suprachiasmatic nucleus (SCN). Circadian oscillations are generated in individual SCN neurons by a molecular regulatory network. Cells oscillate with periods ranging from 20 to 28 h, but at the tissue level, SCN neurons display significant synchrony, suggesting a robust intercellular coupling in which neurotransmitters are assumed to play a crucial role. We present a dynamical model for the coupling of a population of circadian oscillators in the SCN. The cellular oscillator, a three-variable model, describes the core negative feedback loop of the circadian clock. The coupling mechanism is incorporated through the global level of neurotransmitter concentration. Global coupling is efficient to synchronize a population of 10,000 cells. Synchronized cells can be entrained by a 24-h light-dark cycle. Simulations of the interaction between two populations representing two regions of the SCN show that the driven population can be phase-leading. Experimentally testable predictions are: 1), phases of individual cells are governed by their intrinsic periods; and 2), efficient synchronization is achieved when the average neurotransmitter concentration would dampen individual oscillators. However, due to the global neurotransmitter oscillation, cells are effectively synchronized.
在哺乳动物中，控制日常节律的昼夜节律起搏器位于视交叉上核（SCN）。昼夜节律振荡由分子调节网络在单个SCN神经元中产生。细胞的振荡周期在20到28小时之间，但在组织水平上，SCN神经元表现出显著的同步性，这表明存在强大的细胞间耦合，其中神经递质被认为起着关键作用。我们提出了一个关于SCN中一群昼夜节律振荡器耦合的动力学模型。细胞振荡器是一个三变量模型，描述了昼夜节律钟的核心负反馈回路。耦合机制通过神经递质浓度的全局水平来纳入。全局耦合对于同步一万个细胞的群体是有效的。同步的细胞可以被24小时的明暗周期所夹带。对代表SCN两个区域的两个群体之间相互作用的模拟表明，被驱动的群体可以相位领先。可通过实验验证的预测是：1）单个细胞的相位由其固有周期决定；2）当平均神经递质浓度会抑制单个振荡器时，可实现有效的同步。然而，由于神经递质的全局振荡，细胞实际上是同步的。
