Central control of circadian phase in arousal-promoting neurons.

Central control of circadian phase in arousal-promoting neurons.
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DOI:
10.1371/journal.pone.0067173
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Bittman EL
Bittman EL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mahoney CE;Brewer JM;Bittman EL

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下丘脑背内侧/外侧(DMH/LH)细胞产生下丘脑泌素(HCRT),部分通过激活表达酪氨酸羟化酶(TH)的蓝斑(LC)细胞来促进唤醒。视交叉上核(SCN)驱动内源性日常节律,包括睡眠和觉醒的节律。这些昼夜节律振荡是由转录-翻译反馈回路产生的,其中周期(Per)基因构成关键组件。这种细胞自主的分子钟不仅在SCN内运行,而且在其他大脑区域的神经元中也运行。然而,这些神经元的表型和来自起搏器的相位控制信号的性质在很大程度上是未知的。我们使用双荧光原位杂交技术,以评估时钟功能加压素,HCRT和TH细胞的SCN,DMH/LH和LC,分别为雄性叙利亚仓鼠。在第一个实验中,我们发现Per 1在HCRT和TH中的表达在持续黑暗中的动物中振荡,峰值相位滞后于SCN的AVP细胞数小时。在第二个实验中,仓鼠诱导分裂他们的运动节律暴露于恒定的光有不对称的Per 1表达细胞内的中间SCN在6小时前的活动开始(AO)和HCRT细胞9小时前,并在AO。我们没有观察到Per 1在LC中表达偏侧化的证据。我们的结论是,SCN通信昼夜节律阶段HCRT细胞通过偏侧的神经投射,并建议Per 1在LC的表达可能是由全球或双边性质的信号调节。
Cells of the dorsomedial/lateral hypothalamus (DMH/LH) that produce hypocretin (HCRT) promote arousal in part by activation of cells of the locus coeruleus (LC) which express tyrosine hydroxylase (TH). The suprachiasmatic nucleus (SCN) drives endogenous daily rhythms, including those of sleep and wakefulness. These circadian oscillations are generated by a transcriptional-translational feedback loop in which the Period (Per) genes constitute critical components. This cell-autonomous molecular clock operates not only within the SCN but also in neurons of other brain regions. However, the phenotype of such neurons and the nature of the phase controlling signal from the pacemaker are largely unknown. We used dual fluorescent in situ hybridization to assess clock function in vasopressin, HCRT and TH cells of the SCN, DMH/LH and LC, respectively, of male Syrian hamsters. In the first experiment, we found that Per1 expression in HCRT and TH oscillated in animals held in constant darkness with a peak phase that lagged that in AVP cells of the SCN by several hours. In the second experiment, hamsters induced to split their locomotor rhythms by exposure to constant light had asymmetric Per1 expression within cells of the middle SCN at 6 h before activity onset (AO) and in HCRT cells 9 h before and at AO. We did not observe evidence of lateralization of Per1 expression in the LC. We conclude that the SCN communicates circadian phase to HCRT cells via lateralized neural projections, and suggests that Per1 expression in the LC may be regulated by signals of a global or bilateral nature.
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