Memory-enhancing properties of sleep depend on the oscillatory amplitude of norepinephrine.

Celia Kjaerby, Mie Andersen, Natalie Hauglund, Verena Untiet, Camilla Dall, Björn Sigurdsson, Fengfei Ding, Jiesi Feng, Yulong Li, Pia Weikop, Hajime Hirase, Maiken Nedergaard

Nature neuroscience 2022 Aug

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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. © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

Citation

Celia Kjaerby, Mie Andersen, Natalie Hauglund, Verena Untiet, Camilla Dall, Björn Sigurdsson, Fengfei Ding, Jiesi Feng, Yulong Li, Pia Weikop, Hajime Hirase, Maiken Nedergaard. Memory-enhancing properties of sleep depend on the oscillatory amplitude of norepinephrine. Nature neuroscience. 2022 Aug;25(8):1059-1070