NREM2 and Sleep Spindles Are Instrumental to the Consolidation of Motor Sequence Memories

Although numerous studies have convincingly demonstrated that sleep plays a critical role in motor sequence learning (MSL) consolidation, the specific contribution of the different sleep stages in this type of memory consolidation is still contentious. To probe the role of stage 2 non-REM sleep (NREM2) in this process, we used a conditioning protocol in three different groups of participants who either received an odor during initial training on a motor sequence learning task and were re-exposed to this odor during different sleep stages of the post-training night (i.e., NREM2 sleep [Cond-NREM2], REM sleep [Cond-REM], or were not conditioned during learning but exposed to the odor during NREM2 [NoCond]). Results show that the Cond-NREM2 group had significantly higher gains in performance at retest than both the Cond-REM and NoCond groups. Also, only the Cond-NREM2 group yielded significant changes in sleep spindle characteristics during cueing. Finally, we found that a change in frequency of sleep spindles during cued-memory reactivation mediated the relationship between the experimental groups and gains in performance the next day. These findings strongly suggest that cued-memory reactivation during NREM2 sleep triggers an increase in sleep spindle activity that is then related to the consolidation of motor sequence memories.Targeted reactivation of a motor sequence memory through re-exposure with a conditioned olfactory stimulus during the night reveals the specific role of stage 2 non-REM sleep and spindles in the consolidation process.Author Summary: There is ample evidence that sleep contributes to the consolidation (from a labile to a robust state) of a memory trace formed through learning of a new motor sequence, such as piano-playing. Sleep, however, is a complex neurophysiological state comprising several phases, and the role that each phase plays in this memory process remains controversial. To address this issue, we used a conditioning paradigm with human volunteers in which an odor was first associated (or not) with the practice of a motor sequence learning task. The odor was then presented again in one of two different sleep phases—rapid-eye movement (REM) or stage 2 non-REM (NREM2)—during the second half of the night, as a means of facilitating reactivation of the memory trace. As predicted, we found that participants cued with the odor during NREM2 showed greater gains in performance (reflecting better consolidation) the following morning compared with those who were cued during REM sleep or who had not previously been exposed to the odor during training. We also observed that reactivation during NREM2 sleep prompted significant changes in a type of brain activity known as sleep spindles. We conclude that NREM2 sleep—and spindles in particular—contribute critically to the consolidation of motor sequence memories.