Department of Neuroscience, Chronobiology, and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104.
Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2123528119. doi: 10.1073/pnas.2123528119. Epub 2022 Nov 4.
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.
在日常生活中，我们会遇到不可控的压力事件，这些事件会扰乱我们的睡眠。然而，导致非快速眼动睡眠（NREMs）和快速眼动睡眠（REMs）质量下降的潜在神经机制在很大程度上尚不清楚。在这里，我们在小鼠中表明，急性社会心理压力通过增加短暂觉醒（微觉醒[MAs]）、减少睡眠纺锤波和损害 NREMs 期间脑电图纺锤波带中的亚慢振荡来破坏睡眠，同时减少 REMs。这种睡眠质量下降反映在 NREMs 期间蓝斑核（LC）去甲肾上腺素能（NE）神经元活动中的钙瞬变数量增加。在未处理的小鼠中，对 LC-NE 进行光遗传学和化学遗传学激活足以改变与压力相似的睡眠微结构。相反，化学遗传抑制 LC-NE 神经元可减少 NREMs 期间的 MAs，并在压力后使其数量正常化。具体来说，抑制投射到下丘脑视前区（POA）的 LC-NE 神经元可减少 MAs 并增强纺锤波和 REMs。光电极记录显示，刺激 POA 中的 LC-NE 纤维确实抑制了在睡眠纺锤波和 REMs 期间激活以及在 MAs 期间失活的 POA 神经元的尖峰活动。我们的研究结果表明，睡眠期间应激调节 LC-NE 神经元动力学的变化会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。
