Anything but small: Microarousals stand at the crossroad between noradrenaline signaling and key sleep functions

Continuous sleep restores the brain and body, whereas fragmented sleep harms cognition and health. Microarousals (MAs), brief (3- to 15-s-long) wake intrusions into sleep, are clinical markers for various sleep disorders. Recent rodent studies show that MAs during healthy non-rapid eye movement (NREM) sleep are driven by infraslow fluctuations of noradrenaline (NA) in coordination with electrophysiological rhythms, vasomotor activity, cerebral blood volume, and glymphatic flow. MAs are hence part of healthy sleep dynamics, raising questions about their biological roles. We propose that MAs bolster NREM sleep's benefits associated with NA fluctuations, according to an inverted U-shaped curve. Weakened noradrenergic fluctuations, as may occur in neurodegenerative diseases or with sleep aids, reduce MAs, whereas exacerbated fluctuations caused by stress fragment NREM sleep and collapse NA signaling. We suggest that MAs are crucial for the restorative and plasticity-promoting functions of sleep and advance our insight into normal and pathological arousal dynamics from sleep.