Forced desynchronization of dual circadian oscillators within the rat suprachiasmatic nucleus
Forced desynchronization of dual circadian oscillators within the rat suprachiasmatic nucleus
复制标题
DOI：
10.1016/j.cub.2004.04.034
复制
发表时间：
2004-05-04
期刊：
影响因子：
9.2
通讯作者：
Díez-Noguera, A
中科院分区：
文献类型：
--
作者：
de la Iglesia, HO;Cambras, T;Díez-Noguera, A
下丘脑视交叉上核（SCN）[1]中的昼夜节律钟包含多个自主的单细胞昼夜节律振荡器[2]，并且它们的基本细胞内振荡机制开始被识别[3]。不太清楚的是，单个SCN细胞如何创建一个集成的组织起搏器，该起搏器向生物体的其他部分产生连贯的读数。细胞间偶联机制必须协调单个细胞周期，以产生整个动物的平均基因型特异性昼夜节律周期[4，5]。为了在体内非侵入性地分离这种昼夜振荡网络，我们（T.C.和AD- N.）的已经开发出一种实验范例，将动物暴露于具有接近昼夜节律夹带极限的周期的外来光暗（LD）周期[6]。如果不同周期的单个振荡器在网络中松散耦合，也许其中一些振荡器会与外部周期同步，而另一些振荡器则保持不受影响。事实上，暴露于人工短的22小时LD周期的大鼠在个体动物中表达两种具有不同周期长度的稳定昼夜运动活动节律。我们的SCN基因表达在这种条件下的分析表明，这两个运动活动的节奏反映了两个振荡器在解剖定义的腹外侧和背内侧SCN细分的单独活动。我们的“强制去同步”协议允许这两个区域振荡器在体内的第一个稳定的分离，将它们的活动与不同的行为输出相关联，并为理解行为动物的SCN组织和信号传导机制提供了一种强有力的方法。
The circadian clock in the suprachiasmatic nucleus of the hypothalamus (SCN) [1] contains multiple autonomous single-cell circadian oscillators [2] and their basic intracellular oscillatory mechanism is beginning to be identified [3]. Less well understood is how individual SCN cells create an integrated tissue pacemaker that produces a coherent read-out to the rest of the organism. Intercellular coupling mechanisms must coordinate individual cellular periods to generate the averaged, genotype-specific circadian period of whole animals [4, 5]. To noninvasively dissociate this circadian oscillatory network in vivo, we (T.C. and A.D.-N.) have developed an experimental paradigm that exposes animals to exotic light-dark (LD) cycles with periods close to the limits of circadian entrainment [6]. If individual oscillators with different periods are loosely coupled within the network, perhaps some of them would be synchronized to the external cycle while others remain unentrained. In fact, rats exposed to an artificially short 22 hr LD cycle express two stable circadian motor activity rhythms with different period lengths in individual animals. Our analysis of SCN gene expression under such conditions suggests that these two motor activity rhythms reflect the separate activities of two oscillators in the anatomically defined ventrolateral and dorsomedial SCN subdivisions. Our "forced desychronization" protocol has allowed the first stable separation of these two regional oscillators in vivo, correlating their activities to distinct behavioral outputs, and providing a powerful approach for understanding SCN tissue organization and signaling mechanisms in behaving animals.