Taylor Stephanie R, Wang Thomas J, Granados-Fuentes Daniel, Herzog Erik D
Department of Computer Science, Colby College, Waterville, Maine.
Department of Biology, Washington University, St. Louis, Missouri.
J Biol Rhythms. 2017 Feb;32(1):35-47. doi: 10.1177/0748730416680904. Epub 2016 Dec 20.
Although the suprachiasmatic nucleus (SCN) has long been considered the master circadian clock in mammals, the topology of the connections that synchronize daily rhythms among SCN cells is not well understood. We combined experimental and computational methods to infer the directed interactions that mediate circadian synchrony between regions of the SCN. We analyzed PERIOD2 (PER2) expression from SCN slices during and after treatment with tetrodotoxin, allowing us to map connections as cells resynchronized their daily cycling following blockade and restoration of cell-cell communication. Using automated analyses, we found that cells in the dorsal SCN stabilized their periods slower than those in the ventral SCN. A phase-amplitude computational model of the SCN revealed that, to reproduce the experimental results: (1) the ventral SCN had to be more densely connected than the dorsal SCN and (2) the ventral SCN needed strong connections to the dorsal SCN. Taken together, these results provide direct evidence that the ventral SCN entrains the dorsal SCN in constant conditions.
尽管视交叉上核（SCN）长期以来一直被认为是哺乳动物的主生物钟，但SCN细胞之间同步日常节律的连接拓扑结构尚未得到很好的理解。我们结合实验和计算方法来推断介导SCN区域之间昼夜节律同步的定向相互作用。我们分析了用河豚毒素处理期间和处理后SCN切片中的周期蛋白2（PER2）表达，这使我们能够在细胞间通信被阻断和恢复后，随着细胞重新同步其日常循环来绘制连接图。通过自动分析，我们发现背侧SCN中的细胞比腹侧SCN中的细胞更慢地稳定其周期。SCN的相位-振幅计算模型表明，为了重现实验结果：（1）腹侧SCN的连接必须比背侧SCN更密集，并且（2）腹侧SCN需要与背侧SCN有强连接。综上所述，这些结果提供了直接证据，表明在恒定条件下，腹侧SCN会带动背侧SCN。
