Wavelet measurement suggests cause of period instability in mammalian circadian neurons.
Wavelet measurement suggests cause of period instability in mammalian circadian neurons.
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DOI：
10.1177/0748730411409863
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发表时间：
2011-08
影响因子：
3.5
通讯作者：
Petzold LR
中科院分区：
文献类型：
--
作者：
Meeker K;Harang R;Webb AB;Welsh DK;Doyle FJ 3rd;Bonnet G;Herzog ED;Petzold LR
视交叉上核(SCN)中的细胞表现出惊人的精确度，而无论是物理上还是化学上使这些细胞彼此分离，都会导致周期间变异性的显著增加。以前的研究已经将细胞分为心律失常或昼夜节律，我们的小波分析显示，当单个细胞从网络相互作用中移除时，间歇性地表达昼夜节律和/或更长的亚生理周期。我们用BMal1转录抑制分叉附近的非偶联SCN细胞的随机模型再现了非偶联SCN细胞的特征周期分布。这表明未偶联的细胞可能在两种振荡机制之间切换：蛋白质复合体PERCRE对Per和Cry基因表达的间接负反馈以及Clock-BMAL1对BMal1基因表达的负反馈。该模型在这个分叉点附近特别敏感，只需要对BMal1转录抑制进行很小的改变，就可以从耦合的SCN细胞的稳定精度切换到解偶联的单个细胞的不稳定振荡，使这个速率恒定，成为SCN中细胞信号传递的理想靶点。
Cells in the suprachiasmatic nucleus (SCN) display remarkable precision, while either physically or chemically decoupling these cells from each other leads to a dramatic increase in period-to-period variability. Where previous studies have classified cells as either arrhythmic or circadian, our wavelet analysis reveals that individual cells, when removed from network interactions, intermittently express circadian and/or longer infradian periods. We reproduce the characteristic period distribution of uncoupled SCN cells with a stochastic model of the uncoupled SCN cell near a bifurcation in Bmal1 transcription repression. This suggests that the uncoupled cells may be switching between 2 oscillatory mechanisms: the indirect negative feedback of protein complex PER-CRY on the expression of Per and Cry genes, and the negative feedback of CLOCK-BMAL1 on the expression of the Bmal1 gene. The model is particularly sensitive near this bifurcation point, with only a small change in Bmal1 transcription repression needed to switch from the stable precision of coupled SCN cells to the unstable oscillations of decoupled individual cells, making this rate constant, an ideal target for cell signaling in the SCN.
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