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哺乳动物昼夜节律中枢视交叉上核的区域性昼夜周期差异。

Regional circadian period difference in the suprachiasmatic nucleus of the mammalian circadian center.

机构信息

Department of Anatomy and Neurobiology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.

出版信息

Eur J Neurosci. 2013 Sep;38(6):2832-41. doi: 10.1111/ejn.12308. Epub 2013 Jul 22.

Abstract

The suprachiasmatic nucleus (SCN) is the mammalian circadian rhythm center. Individual oscillating neurons have different endogenous circadian periods, but they are usually synchronized by an intercellular coupling mechanism. The differences in the period of each oscillating neuron have been extensively studied; however, the clustering of oscillators with similar periods has not been reported. In the present study, we artificially disrupted the intercellular coupling among oscillating neurons in the SCN and observed regional differences in the periods of the oscillating small-latticed regions of the SCN using a transgenic rat carrying a luciferase reporter gene driven by regulatory elements from a per2 clock gene (Per2::dluc rat). The analysis divided the SCN into two regions--aregion with periods shorter than 24 h (short-period region, SPR) and another with periods longer than 24 h (long-period region, LPR). The SPR was located in the smaller medial region of the dorsal SCN, whereas the LPR occupied the remaining larger region. We also found that slices containing the medial region of the SCN generated shorter circadian periods than slices that contained the lateral region of the SCN. Interestingly, the SPR corresponded well with the region where the SCN phase wave is generated. We numerically simulated the relationship between the SPR and a large LPR. A mathematical model of the SCN based on our findings faithfully reproduced the kinetics of the oscillators in the SCN in synchronized conditions, assuming the existence of clustered short-period oscillators.

摘要

视交叉上核(SCN)是哺乳动物的生物钟中心。单个振荡神经元具有不同的内源性生物钟周期,但它们通常通过细胞间耦合机制同步。每个振荡神经元周期的差异已经得到了广泛的研究;然而,具有相似周期的振荡器的聚类尚未报道。在本研究中,我们人为地破坏了 SCN 中振荡神经元之间的细胞间耦合,并使用携带由 Per2 时钟基因的调控元件驱动的荧光素酶报告基因的转基因大鼠(Per2::dluc 大鼠)观察到 SCN 的振荡小晶格区域的周期的区域差异。分析将 SCN 分为两个区域 - 周期短于 24 小时的区域(短周期区域,SPR)和周期长于 24 小时的区域(长周期区域,LPR)。SPR 位于 SCN 的较小的背内侧区域,而 LPR 占据了剩余的较大区域。我们还发现包含 SCN 内侧区域的切片产生的生物钟周期短于包含 SCN 外侧区域的切片。有趣的是,SPR 与 SCN 相位波产生的区域非常吻合。我们数值模拟了 SPR 和较大的 LPR 之间的关系。基于我们的发现的 SCN 数学模型在同步条件下忠实地再现了 SCN 中的振荡器动力学,假设存在聚类的短周期振荡器。

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