The breathing cycle gates memory reactivation during human NREM sleep

Sleep-dependent memory consolidation relies on the precise coordination of slow oscillations (SOs) and spindles. Respiration has recently emerged as a potential pacemaker of this coordination, but whether it thereby shapes memory processes during sleep remains unknown. Here, we used closed-loop targeted memory reactivation (TMR) in humans (N = 25) to target auditory cues to either each participant's SO-spindle-favored respiratory phase (preferred-phase cueing) or the opposite phase (antiphase cueing). Preferred-phase cueing enhanced associative memory relative to antiphase cueing and promoted more precise spindle alignment to SO up-states. Respiratory phase also shaped the timing of reactivation: preferred-phase cues aligned category-specific reactivation with the ensuing SO up-state, whereas antiphase cues delayed reactivation to later SO-spindle complexes occurring at a similar respiratory phase. These findings identify breathing as an endogenous timing signal that organizes the SO-spindle windows in which memory reactivation unfolds, thereby structuring sleep-dependent consolidation.