Differential contributions of intra-cellular and inter-cellular mechanisms to the spatial and temporal architecture of the suprachiasmatic nucleus circadian circuitry in wild-type, cryptochrome-null and vasoactive intestinal peptide receptor 2-null mutant mice
Differential contributions of intra-cellular and inter-cellular mechanisms to the spatial and temporal architecture of the suprachiasmatic nucleus circadian circuitry in wild-type, cryptochrome-null and vasoactive intestinal peptide receptor 2-null mutant mice
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DOI：
10.1111/ejn.12631
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发表时间：
2014-08-01
影响因子：
3.4
通讯作者：
Silver, R.
中科院分区：
文献类型：
--
作者：
Pauls, S.;Foley, N. C.;Silver, R.
为了充当强大的内部生物钟，哺乳动物视交叉上核（SCN）单个神经元的细胞自主分子和电生理活动在时间和神经解剖空间上进行协调。尽管神经元之间的化学和电互连对于这种电路级编排至关重要，但它们为赋予整体信号鲁棒性而发挥作用的特征尚不清楚。为了解决这个问题，我们应用了多种方法来解构昼夜节律异常小鼠的器官切片中昼夜节律振荡的空间和时间组织之间的相互作用。我们研究了缺乏隐花色素基因（Cry1和Cry2）的小鼠的视交叉上核（Cry1和Cry2），这对于细胞自主振荡至关重要，以及缺乏血管活性肠肽受体2（VPAC2-null）的小鼠的视交叉上核（VPAC2-null），这是电路水平整合所必需的，以便将生物机制映射到所揭示的振荡特征。野生型小鼠的 SCN 显示 PER2::LUC 生物发光谱的时间节律与规则重复的空间组织振荡之间存在密切联系。 Cry-null SCN 具有稳定的空间组织，但缺乏时间组织，而在 VPAC2-null SCN 中，一些样本在缺乏空间组织的情况下表现出时间组织。结果表明，空间和时间组织是可分离的，它们可能具有不同的机制起源（细胞自主信号与神经元间信号传导），并且两者都是维持整个视交叉上核稳健且有组织的昼夜节律所必需的。因此，这项研究提供的证据表明，在空间组织簇中揭示的神经元回路的连贯涌现特性对于 SCN 的起搏功能至关重要。
To serve as a robust internal circadian clock, the cell-autonomous molecular and electrophysiological activities of the individual neurons of the mammalian suprachiasmatic nucleus (SCN) are coordinated in time and neuroanatomical space. Although the contributions of the chemical and electrical interconnections between neurons are essential to this circuit-level orchestration, the features upon which they operate to confer robustness to the ensemble signal are not known. To address this, we applied several methods to deconstruct the interactions between the spatial and temporal organisation of circadian oscillations in organotypic slices from mice with circadian abnormalities. We studied the SCN of mice lacking Cryptochrome genes (Cry1 and Cry2), which are essential for cell-autonomous oscillation, and the SCN of mice lacking the vasoactive intestinal peptide receptor 2 (VPAC2-null), which is necessary for circuit-level integration, in order to map biological mechanisms to the revealed oscillatory features. The SCN of wild-type mice showed a strong link between the temporal rhythm of the bioluminescence profiles of PER2::LUC and regularly repeated spatially organised oscillation. The Cry-null SCN had stable spatial organisation but lacked temporal organisation, whereas in VPAC2-null SCN some specimens exhibited temporal organisation in the absence of spatial organisation. The results indicated that spatial and temporal organisation were separable, that they may have different mechanistic origins (cell-autonomous vs. interneuronal signaling) and that both were necessary to maintain robust and organised circadian rhythms throughout the SCN. This study therefore provided evidence that the coherent emergent properties of the neuronal circuitry, revealed in the spatially organised clusters, were essential to the pacemaking function of the SCN.