Cellular Clocks in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior Rhythm
Cellular Clocks in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior Rhythm
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DOI：
10.1016/j.neuron.2015.02.005
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发表时间：
2015-03-04
期刊：
影响因子：
16.2
通讯作者：
Sakurai, Takeshi
中科院分区：
文献类型：
--
作者：
Mieda, Michihiro;Ono, Daisuke;Sakurai, Takeshi
视交叉上核（SCN）是哺乳动物的主要昼夜节律起搏器，是由多种类型神经元组成的网络结构。在这里，我们报告说，产生精氨酸加压素（AVP）的神经元特异的 Bmal1 缺失的小鼠表现出自由奔跑期和行为节律的活动时间显着延长。当暴露于突然提前 8 小时的光/暗循环时，这些小鼠比对照小鼠恢复得更快。在这些小鼠中，参与细胞间通讯的基因（包括 Avp、Prokineticin 2 和 Rgs16）的昼夜节律表达在 AVP 神经元占主导地位的背侧 SCN 中急剧减少。在切片中，背侧 SCN 细胞显示 PER2::LUC 振荡减弱，且周期高度可变且延长。因此，AVP 神经元的 Bmal1 依赖性振荡器可以调节 SCN 网络的耦合，通过调节对这些神经元的网络特性重要的多种因子的表达，最终耦合早晨和晚上的行为节律。
The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, is a network structure composed of multiple types of neurons. Here, we report that mice with a Bmal1 deletion specific to arginine vasopressin (AVP)-producing neurons showed marked lengthening in the free-running period and activity time of behavior rhythms. When exposed to an abrupt 8-hr advance of the light/dark cycle, these mice reentrained faster than control mice did. In these mice, the circadian expression of genes involved in intercellular communications, including Avp, Prokineticin 2, and Rgs16, was drastically reduced in the dorsal SCN, where AVP neurons predominate. In slices, dorsal SCN cells showed attenuated PER2::LUC oscillation with highly variable and lengthened periods. Thus, Bmal1-dependent oscillators of AVP neurons may modulate the coupling of the SCN network, eventually coupling morning and evening behavioral rhythms, by regulating expression of multiple factors important for the network property of these neurons.