Sleep Promotes Learning-Induced Synapse Formation in the Motor Cortex

Sleep is essential for learning and memory consolidation, particularly in modulating synaptic connections crucial for long-term memory formation. However, the precise mechanisms by which sleep affects synaptic plasticity remain unclear. A study by Yang et al., published in Science Advances on July 31, 2019, investigated how sleep influences the remodeling of postsynaptic dendritic spines induced by motor learning in the mouse primary motor cortex. The research revealed that sleep following learning promotes new spine formation on distinct sets of apical tuft branches of individual layer V pyramidal neurons, and this sleep-dependent, branch-specific spine formation facilitates the survival of these new spines during subsequent learning, contributing to long-term memory storage.

The study observed that rotarod motor learning enhances dendritic spine formation on apical tuft dendrites of layer V pyramidal neurons in the motor cortex within two days. Notably, the formation rate of new spines in trained mice was significantly higher within six hours after training compared to untrained controls. To investigate the role of sleep in this process, the researchers compared spine formation in mice that were trained and allowed to sleep undisturbed with mice that were sleep-deprived after training. They found that sleep deprivation significantly reduced learning-induced spine formation, particularly on branches that exhibited high spine formation rates. Furthermore, this reduction in spine formation could not be compensated for by additional training or subsequent sleep.

The study also investigated the fate of new spines formed during 8 hours with or without post-training sleep. The survival of new spines on branches with high spine formation was significantly higher during the next day in mice with sleep after learning compared to those without. This finding suggests that sleep contributes to the formation of persistent new spines on these branches, which correlates with motor skill retention.

To delve deeper into the mechanisms underlying sleep-dependent spine formation, the researchers examined the role of REM and NREM sleep. Interestingly, REM sleep deprivation did not disrupt branch-specific spine formation induced by learning. However, they found that neurons associated with wakeful motor experience were reactivated in the motor cortex during NREM sleep. Furthermore, blocking NMDA receptors, which are crucial for neuronal activity, reduced both neuronal reactivation during NREM sleep and branch-specific spine formation.

The researchers then explored the relationship between the extent of neuronal reactivation and branch-specific spine formation. They found that retraining mice with a different motor task reduced the reactivation of neurons associated with the initial training and also led to a decrease in spine formation on branches that showed high spine formation after the initial training. These results suggest that neuronal reactivation during NREM sleep is involved in promoting branch-specific spine formation.

Overall, this study provides compelling evidence that sleep after motor learning promotes the formation of new dendritic spines on specific branches of neurons in the motor cortex. This sleep-dependent, branch-specific spine formation facilitates the survival of these spines during subsequent learning and contributes to long-term memory storage. These findings shed light on the crucial role of sleep in enhancing learning and memory consolidation and provide valuable insights into the underlying mechanisms of synaptic plasticity.