A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances.
A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances.
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DOI：
10.1073/pnas.2123528119
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发表时间：
2022-11-08
影响因子：
11.1
通讯作者：
Chung, Shinjae
中科院分区：
文献类型：
--
作者：
Antila, Hanna;Kwak, Iris;Choi, Ashley;Pisciotti, Alexa;Covarrubias, Ivan;Baik, Justin;Eisch, Amelia;Beier, Kevin;Thomas, Steven;Weber, Franz;Chung, Shinjae
高质量的睡眠对我们的健康至关重要。睡眠障碍会对我们的身心健康产生负面影响。在这里，我们表明，小鼠的急性心理社会压力通过引起频繁的觉醒，扰乱脑电图的缓慢（10分钟）振荡和抑制REM来扰乱睡眠。这些变化反映在NREM期间蓝斑（LC-NE）中去甲肾上腺素能神经元的频繁激活中。激活LC-NE神经元会破坏睡眠质量，类似于压力，而在压力后抑制它们可以部分通过投射到视前区（一个关键的睡眠中心）来改善睡眠。我们的研究表明，LC-NE神经元及其与下丘脑睡眠神经元的相互作用协调了睡眠微结构，并在介导压力对睡眠的负面影响方面发挥了至关重要的作用。在我们的日常生活中，我们会遇到无法控制且有压力的事件，这些事件会扰乱我们的睡眠。然而，降低非快速眼动睡眠（NREM）和REM睡眠质量的潜在神经机制在很大程度上是未知的。在这里，我们在小鼠中显示，急性心理社会应激通过增加短暂觉醒（微觉醒[MA]），减少睡眠纺锤波，并在NREM期间损害脑电图纺锤波带的次声振荡，同时减少REM来扰乱睡眠。这种睡眠质量差反映在NREM期间蓝斑（LC）中去甲肾上腺素能（NE）神经元活动的钙瞬变数量增加。在幼稚小鼠中光致和化学发生LC-NE激活足以改变睡眠微结构，类似于压力。相反，化学发生抑制LC-NE神经元减少了NREM期间的MA，并在应激后使其数量正常化。特异性抑制LC-NE神经元投射到下丘脑视前区（POA）减少MA和增强纺锤体和REM后的压力。光电极记录显示，刺激LC-NE纤维在POA确实抑制了POA神经元的尖峰活动，这些神经元在睡眠纺锤波和REM期间被激活，在MA期间被灭活。我们的研究结果表明，压力调节LC-NE神经元在睡眠过程中的动态变化对睡眠质量产生负面影响，部分原因是它们与POA的相互作用。
Good-quality sleep is essential for our well-being. Sleep disturbances can negatively affect our mental and physical health. Here, we show that acute psychosocial stress in mice disrupts sleep, by causing frequent arousals, disrupting slow (∼minute) oscillations in the electroencephalogram and suppressing REMs. These changes are reflected in a frequent activation of noradrenergic neurons in the locus coeruleus (LC-NE) during NREMs. Activating LC-NE neurons disrupted sleep quality similar to stress, while inhibiting them after stress improved sleep partially through their projections to the preoptic area, a crucial sleep center. Our study reveals that LC-NE neurons and their interactions with hypothalamic sleep neurons orchestrate the sleep microarchitecture and play a crucial role in mediating the negative impact of stress on sleep. In our daily life, we are exposed to uncontrollable and stressful events that disrupt our sleep. However, the underlying neural mechanisms deteriorating the quality of non-rapid eye movement sleep (NREMs) and REM sleep are largely unknown. Here, we show in mice that acute psychosocial stress disrupts sleep by increasing brief arousals (microarousals [MAs]), reducing sleep spindles, and impairing infraslow oscillations in the spindle band of the electroencephalogram during NREMs, while reducing REMs. This poor sleep quality was reflected in an increased number of calcium transients in the activity of noradrenergic (NE) neurons in the locus coeruleus (LC) during NREMs. Opto- and chemogenetic LC-NE activation in naïve mice is sufficient to change the sleep microarchitecture similar to stress. Conversely, chemogenetically inhibiting LC-NE neurons reduced MAs during NREMs and normalized their number after stress. Specifically inhibiting LC-NE neurons projecting to the preoptic area of the hypothalamus (POA) decreased MAs and enhanced spindles and REMs after stress. Optrode recordings revealed that stimulating LC-NE fibers in the POA indeed suppressed the spiking activity of POA neurons that are activated during sleep spindles and REMs and inactivated during MAs. Our findings reveal that changes in the dynamics of the stress-regulatory LC-NE neurons during sleep negatively affect sleep quality, partially through their interaction with the POA.
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DOI：
10.1523/jneurosci.1809-08.2008
发表时间：
2008-10-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cano G;Mochizuki T;Saper CB
通讯作者：
Saper CB
影响因子：
16.6
作者：
Bandarabadi M;Herrera CG;Gent TC;Bassetti C;Schindler K;Adamantidis AR
通讯作者：
Adamantidis AR
影响因子：
3.7
作者：
Eschenko, Oxana;Sara, Susan J.
通讯作者：
Sara, Susan J.
影响因子：
5.3
作者：
Funk, Chadd M.;Peelman, Kayla;Tononi, Giulio
通讯作者：
Tononi, Giulio
影响因子：
16.2
作者：
Feng, Jiesi;Zhang, Changmei;Li, Yulong
通讯作者：
Li, Yulong