Circadian regulation of mouse suprachiasmatic nuclei neuronal states shapes responses to orexin.
Circadian regulation of mouse suprachiasmatic nuclei neuronal states shapes responses to orexin.
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DOI：
10.1111/ejn.13506
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Piggins HD
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文献类型：
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作者：
Belle MD;Piggins HD
我们对昼夜节律和体内平衡脑回路如何相互作用以暂时组织生理和行为的了解是有限的。下丘脑外侧食欲素（OXA）神经元控制唤醒和食欲状态，而视交叉上核（SCN）神经元作为主昼夜节律钟的研究已经取得进展。在白天，SCN神经元的自发静息膜电位（RMP）表现出异质性，一些神经元严重去极化（高兴奋）并停止火动作电位（APs），而另一些神经元则处于中度RMP和火动作电位。有趣的是，白天阶段是SCN时钟最容易受到觉醒影响的阶段，但目前尚不清楚SCN神经元兴奋性状态的异质性是否以及如何影响它们对觉醒信号（如OXA）的反应。在全细胞记录中，我们发现在白天，OXA募集GABA - GABAA受体信号来抑制高兴奋沉默和中度超极化AP -放电的SCN神经元的RMP。在AP -放电神经元中，OXA超极化并使这些SCN细胞沉默，而在高兴奋的沉默神经元中，OXA抑制这些细胞的RMP并引起AP -放电、去极化低振幅膜振荡或在RMP降低时持续沉默。这些结果证明了SCN神经元的静息状态如何决定它们对OXA的反应，并说明了这种与觉醒相关的神经化学物质的抑制作用可以触发矛盾的AP放电。
Our knowledge of how circadian and homeostatic brain circuits interact to temporally organize physiology and behavior is limited. Progress has been made with the determination that lateral hypothalamic orexin (OXA) neurons control arousal and appetitive states, while suprachiasmatic nuclei (SCN) neurons function as the master circadian clock. During the day, SCN neurons exhibit heterogeneity in spontaneous resting membrane potential (RMP), with some neurons becoming severely depolarized (hyperexcited) and ceasing to fire action potentials (APs), while other neurons rest at moderate RMP and fire APs. Intriguingly, the day phase is when the SCN clock is most readily influenced by arousal, but it is unclear if and how heterogeneity in the excitability state of SCN neurons shapes their response to arousal signals, such as OXA. In whole‐cell recordings we show that during the day OXA recruits GABA‐GABAA receptor signaling to suppress the RMP of hyperexcited silent as well as moderately hyperpolarized AP‐firing SCN neurons. In the AP‐firing neurons, OXA hyperpolarized and silenced these SCN cells, while in the hyperexcited silent neurons OXA suppressed the RMP of these cells and evoked either AP‐firing, depolarized low‐amplitude membrane oscillations, or continued silence at a reduced RMP. These results demonstrate how the resting state of SCN neurons determines their response to OXA, and illustrate that the inhibitory action of this neurochemical correlate of arousal can trigger paradoxical AP firing.