Journal
NATURE NEUROSCIENCE
Volume 25, Issue 8, Pages 1059-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41593-022-01102-9
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Funding
- Lundbeck Foundation [R386-2021-165]
- Independent Research Council Denmark [7016-00324A]
- Augustinus Foundation [16-3735]
- Novo Nordisk Foundation [NNF20OC0066419]
- US Department of Health & Human Services, National Institutes of Health (NIH) [R01AT011439]
- US Department of Defense, Army Research Office [W911NF1910280]
- Simons Foundation [811237]
- Adelson Foundation
- National Key R&D Program of China [2021YFF0502904]
- National Natural Science Foundation of China [31925017, 31871087]
- NIH BRAIN Initiative [1U01NS113358, 1U01NS120824]
- FENG Foundation
- U.S. Department of Defense (DOD) [W911NF1910280] Funding Source: U.S. Department of Defense (DOD)
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Kjaerby and Andersen et al. demonstrate the important role of norepinephrine (NE) in shaping sleep micro-architecture. NE oscillates during sleep and its amplitude affects memory consolidation and awakenings. Micro-arousals are generated in a periodic pattern during NREM sleep, while NE oscillations drive spindles. The amplitude of NE oscillations plays a crucial role in sleep micro-architecture and memory performance.
Kjaerby and Andersen et al. show that norepinephrine (NE) plays profound roles in shaping sleep micro-architecture. NE slowly oscillates during sleep, with NE oscillatory amplitude being a major determinant of spindle-dependent memory consolidation and awakenings. 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.
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