GABA networks destabilize genetic oscillations in the circadian pacemaker.

GABA networks destabilize genetic oscillations in the circadian pacemaker.
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DOI:
10.1016/j.neuron.2013.04.003
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发表时间:
2013-06-05
期刊:
影响因子:
16.2
通讯作者:
Herzog ED
Herzog ED
中科院分区:
医学1区
文献类型:
--
作者:
Freeman GM Jr;Krock RM;Aton SJ;Thaben P;Herzog ED

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自然界中有大量的耦合振子系统。它们如何在不同条件下建立稳定的相位关系至关重要。哺乳动物视交叉上核(SCN)是一个自我维持、同步的昼夜节律振荡器网络,协调生理和行为的日常节律。为了阐明调节昼夜节律同步的潜在拓扑结构和信号机制,我们连续数天区分数百个SCN神经元的放电。使用一种新的分析方法来识别基于其放电变化的神经元之间的功能相互作用,我们表征了由快速,兴奋性和抑制性连接组成的GABA能网络,该网络在几天内都是稳定的,并且强度随时间变化。通过监测PERIOD2蛋白表达,我们提供了第一个证据,这些毫秒级的相互作用积极反对昼夜节律同步和注入抖动到日常节奏。这些结果提供了一种新的机制,昼夜节律振荡器可以调整它们的相位关系,在不同的环境条件下。
Systems of coupled oscillators abound in nature. How they establish stable phase relationships under diverse conditions is fundamentally important. The mammalian suprachiasmatic nucleus (SCN) is a self-sustained, synchronized network of circadian oscillators that coordinates daily rhythms in physiology and behavior. To elucidate the underlying topology and signaling mechanisms that modulate circadian synchrony, we discriminated the firing of hundreds of SCN neurons continuously over days. Using a novel analysis method to identify functional interactions between neurons based on changes in their firing, we characterized a GABAergic network comprised of fast, excitatory and inhibitory connections that is both stable over days and changes in strength with time of day. By monitoring PERIOD2 protein expression, we provide the first evidence that these millisecond-level interactions actively oppose circadian synchrony and inject jitter into daily rhythms. These results provide a new mechanism by which circadian oscillators can tune their phase relationships under different environmental conditions.
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