Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC2-signaling deficient mice.
Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC2-signaling deficient mice.
复制标题
DOI：
10.1038/srep14044
复制
发表时间：
2015-09-15
影响因子：
4.6
通讯作者：
Piggins HD
中科院分区：
文献类型：
--
作者：
Hughes AT;Croft CL;Samuels RE;Myung J;Takumi T;Piggins HD
视交叉上核(SCN)中的单个神经元包含一个细胞内的分子时钟，并使用细胞间信号来同步它们的计时活动，从而使SCN能够协调大脑的生理和行为。神经肽血管活性肠肽(VIP)及其VPAC2受体构成了SCN细胞间信号系统的关键组成部分，对细胞偶联起着关键的控制作用。细胞内时钟或细胞间神经肽信号机制的靶向性突变，如VIP-VPAC2信号，可导致SCN神经元时钟的去同步化和行为节律的丧失。时间生物学的一个重要目标是开发干预措施来纠正昼夜节律计时的缺陷。在这里，我们表明，长期暴露在持续的光促进SCN时钟细胞之间的同步性和~24 h节律的表达在小鼠的行为中，其中细胞间信号通过VIP-VPAC2信号的丢失而中断。这项研究强调了SCN同步性对于行为节律表达的重要性，并揭示了如何使用外部环境中的非侵入性操作来克服这一重要大脑系统中的神经化学通信缺陷。
Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system.