Sleep has a complex micro-architecture, encompassing micro-arousals, sleep spindles and transitions between sleep stages. Fragmented sleep impairs memory consolidation, whereas spindle-rich and delta-rich non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep promote it. However, the relationship between micro-arousals and memory-promoting aspects of sleep remains unclear. In this study, we used fiber photometry in mice to examine how release of the arousal mediator norepinephrine (NE) shapes sleep micro-architecture. Here we show that micro-arousals are generated in a periodic pattern during NREM sleep, riding on the peak of locus-coeruleus-generated infraslow oscillations of extracellular NE, whereas descending phases of NE oscillations drive spindles. The amplitude of NE oscillations is crucial for shaping sleep micro-architecture related to memory performance: prolonged descent of NE promotes spindle-enriched intermediate state and REM sleep but also associates with awakenings, whereas shorter NE descents uphold NREM sleep and micro-arousals. Thus, the NE oscillatory amplitude may be a target for improving sleep in sleep disorders.

睡眠具有复杂的微结构，包括微觉醒、睡眠纺锤波和睡眠阶段之间的转换。碎片化睡眠会损害记忆巩固，而富含纺锤体和富含三角洲的非快速眼动 (NREM) 睡眠和快速眼动 (REM) 睡眠会促进记忆巩固。然而，微觉醒与睡眠的记忆促进方面之间的关系仍不清楚。在这项研究中，我们在小鼠身上使用纤维光度法来检查唤醒介质去甲肾上腺素 (NE) 的释放如何塑造睡眠微结构。在这里，我们表明微觉醒是在 NREM 睡眠期间以周期性模式产生的，骑在蓝斑产生的胞外 NE 次低振荡的峰值上，而 NE 振荡的下降阶段驱动纺锤波。NE 振荡的幅度对于塑造与记忆性能相关的睡眠微结构至关重要：NE 的长时间下降促进纺锤体丰富的中间状态和 REM 睡眠，但也与觉醒相关，而较短的 NE 下降维持 NREM 睡眠和微觉醒。因此，NE 振荡幅度可能是改善睡眠障碍中睡眠的目标。