Characterization of orderly spatiotemporal patterns of clock gene activation in mammalian suprachiasmatic nucleus.

Characterization of orderly spatiotemporal patterns of clock gene activation in mammalian suprachiasmatic nucleus.
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哺乳动物上颈部核中时钟基因激活的有序时空模式的表征。

DOI:
10.1111/j.1460-9568.2011.07682.x
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发表时间:
2011-05
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Silver R
Silver R
中科院分区:
其他
文献类型:
--
作者:
Foley NC;Tong TY;Foley D;Lesauter J;Welsh DK;Silver R

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由于我们可以观察到单个细胞和整个组织中的振荡,因此视交叉上核(SCN)在哺乳动物大脑中提供了一个独特的系统,用于分析单个细胞及其网络。虽然SCN的分散细胞孤立地维持昼夜节律振荡,但它们是不稳定的振荡器,需要网络相互作用才能实现稳健的循环。使用聚类分析来评估PERIOD2 α荧光素酶(PER2 α LUC)敲入小鼠的急性脑切片中的生物发光,以及在不同昼夜节律时间收获的动物的SCN的免疫化学,我们评估了PER2的时空激活模式,以探索在组织水平上出现的相干振荡。结果表明,昼夜节律振荡的特点是一个稳定的日常周期PER2的表达,涉及有序的串行激活特定的SCN亚区,然后是一个沉默的时间间隔,与SCN的左侧和右侧之间的基本对称。在活体切片中鉴定的簇的生物学意义通过在固定的免疫化学染色的脑切片中LUC和PER 2的共表达来证实,LUC表达的时空模式类似于在生物发光切片的簇分析中所揭示的。我们的结论是,单个神经元内PER 2表达的精确时间取决于它们在细胞核内的位置,并且SCN内的一小群神经元产生了独特且可识别的亚区域。我们建议,这些子区域的串行激活的基础上的SCN的日常节奏的鲁棒性和弹性。
Because we can observe oscillation within individual cells and in the tissue as a whole, the suprachiasmatic nucleus (SCN) presents a unique system in the mammalian brain for the analysis of individual cells and the networks of which they are a part. While dispersed cells of the SCN sustain circadian oscillations in isolation, they are unstable oscillators that require network interactions for robust cycling. Using cluster analysis to assess bioluminescence in acute brain slices from PERIOD2∷Luciferase (PER2∷LUC) knockin mice, and immunochemistry of SCN from animals harvested at various circadian times, we assessed the spatiotemporal activation patterns of PER2 to explore the emergence of a coherent oscillation at the tissue level. The results indicate that circadian oscillation is characterized by a stable daily cycle of PER2 expression involving orderly serial activation of specific SCN subregions, followed by a silent interval, with substantial symmetry between the left and right side of the SCN. The biological significance of the clusters identified in living slices was confirmed by co-expression of LUC and PER2 in fixed, immunochemically stained brain sections, with the spatiotemporal pattern of LUC expression resembling that revealed in the cluster analysis of bioluminescent slices. We conclude that the precise timing of PER2 expression within individual neurons is dependent on their location within the nucleus, and that small groups of neurons within the SCN give rise to distinctive and identifiable subregions. We propose that serial activation of these subregions is the basis of robustness and resilience of the daily rhythm of the SCN.
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影响因子: 64.8
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