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光遗传刺激 VIP 能神经元可诱导哺乳动物生物钟呈现光周期样变化。

Optogenetic stimulation of VIPergic SCN neurons induces photoperiodic-like changes in the mammalian circadian clock.

机构信息

Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.

出版信息

Eur J Neurosci. 2021 Nov;54(9):7063-7071. doi: 10.1111/ejn.15442. Epub 2021 Oct 4.

Abstract

Circadian clocks play key roles in how organisms respond to and even anticipate seasonal change in day length, or photoperiod. In mammals, photoperiod is encoded by the central circadian pacemaker in the brain, the suprachiasmatic nucleus (SCN). The subpopulation of SCN neurons that secrete the neuropeptide VIP mediates the transmission of light information within the SCN neural network, suggesting a role for these neurons in circadian plasticity in response to light information that has yet to be directly tested. Here, we used in vivo optogenetic stimulation of VIPergic SCN neurons followed by ex vivo PERIOD 2::LUCIFERASE (PER2::LUC) bioluminescent imaging to test whether activation of this SCN neuron subpopulation can induce SCN network changes that are hallmarks of photoperiodic encoding. We found that optogenetic stimulation designed to mimic a long photoperiod indeed altered subsequent SCN entrained phase, increased the phase dispersal of PER2 rhythms within the SCN network, and shortened SCN free-running period-similar to the effects of a true extension of photoperiod. Optogenetic stimulation also induced analogous changes on related aspects of locomotor behaviour in vivo. Thus, selective activation of VIPergic SCN neurons induces photoperiodic network plasticity in the SCN that underpins photoperiodic entrainment of behaviour.

摘要

生物钟在生物如何应对甚至预测季节变化的日照时长(或光周期)方面起着关键作用。在哺乳动物中,光周期由大脑中的中央生物钟起搏器——视交叉上核(SCN)编码。分泌神经肽 VIP 的 SCN 神经元亚群介导了 SCN 神经网络内光信息的传递,这表明这些神经元在光信息引起的生物钟可塑性中发挥作用,但这一作用尚未得到直接验证。在这里,我们使用体内光遗传学刺激 VIP 能 SCN 神经元,然后进行体外 PERIOD 2::LUCIFERASE(PER2::LUC)生物发光成像,以测试这种 SCN 神经元亚群的激活是否可以诱导 SCN 网络变化,这些变化是光周期编码的特征。我们发现,设计用来模拟长光周期的光遗传学刺激确实改变了随后的 SCN 被同步的相位,增加了 SCN 网络内 PER2 节律的相位分散,并缩短了 SCN 自由运行周期——类似于真正延长光周期的效果。光遗传学刺激也在体内的相关运动行为方面诱导了类似的变化。因此,选择性激活 VIP 能 SCN 神经元会诱导 SCN 中的光周期网络可塑性,从而为行为的光周期同步提供基础。

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