While you were sleeping: Neural reactivations promote motor learning

Do you recall that moment when you first learned to ride a bike? After days of practice, it finally clicked. Almost effortlessly, your legs cycled in perfect harmony as you maneuvered gracefully around turns and maintained impeccable balance. You may have learned this skill decades ago but it will likely stick with you for the rest of your life. How did your brain accomplish this remarkable feat of transforming a series of forced and foreign actions into an automatic, fluid movement sequence? A new PLOS Biology study by Dr. Dhakshin Ramanathan and colleagues explored the neural substrates of motor memory acquisition, reporting that reactivation of task-related neural activity patterns during sleep promotes motor skill learning in mice.

Sleep enhances motor learning

To evaluate motor learning, the researchers trained mice to perform a task in which they had to reach for a food pellet. Since sleep is known to be important for memory consolidation, the mice were allowed to sleep before and again after the reach task. The mice performed the task a second time after sleeping to assess how sleep affected their performance. Accuracy on the reaching task improved over the course of the first training period, whereas the mice responded more quickly after sleeping; hence, “online learning” (during the task) improved accuracy and “offline learning” (while sleeping) improved speed. No changes occurred when the mice were sleep-deprived between task sessions, pinpointing sleep – rather than the passage of time – as the source of the performance boost.

Sleep-dependent neural changes

The researchers next explored the neurophysiological basis for this sleep-dependent learning, recording neural activity from the forelimb area of motor cortex. As co-author Dr. Karunesh Ganguly explained,

“Studies had previously studied hippocampal-based memory systems. It remained unclear specifically how the motor system (i.e., procedural memory) processes memories during sleep.”

When the mice performed the task the second time, after sleeping, the onset of neural firing (time-locked to the reach) peaked earlier, and this activity was more strongly modulated by the task. Notably, firing onset did not change after sleep deprivation, confirming that sleep was necessary for this temporal shift in the neural response.

Learning-related reactivation

Elsewhere in the cortex and hippocampus, during rest neurons will fire in a particular sequence matching the temporal pattern during a prior experience, an event known as “replay” that is thought to support formation of memory for that experience. The researchers speculated that reactivation or replay in motor cortex may similarly promote motor learning. Neural activity patterns identified from the reach task were more prevalent during sleep after the task, showing – as predicted – reactivation of task-related activity after motor learning. When mice performed the reach task on multiple days, over the course of all days the degree of reactivation during sleep correlated with reduced reaction time, linking stronger neural reactivation with behavioral improvements.

Since the authors observed neural reactivation during motor learning, they next wondered whether the temporal sequence of this reactivation may be an important element of the memory code. The neural activation pattern during sleep more closely matched the task-related activity pattern after learning than before, although some of the temporal information in the sleep sequence was lost. Although prior studies have shown a role for hippocampal or cortical replay in memory consolidation, Dr. Ganguly raises the important distinctions that here, they “did not find evidence of ‘replay’ (i.e., sequences) but ‘reactivation’ (i.e., synchronous bursts).”

Learning-related plasticity was evident even at the single neuron level. Those neurons with the highest task-related activity were most strongly reactivated during sleep, and those showing the strongest reactivation also happened to show the most dramatic shift in the onset of their response to reaching. The authors speculate that this increased temporal coupling of neural activity to the task could facilitate binding the neurons into a distributed “movement complex” that aids formation of the motor memory.

Locking to spindles and slow waves for widespread plasticity 

Burst of high-frequency activity – known as spindles – and slow wave oscillations have both been implicated in offline learning. If task-related reactivations during sleep are important for memory consolidation, the authors reasoned, they may be temporally linked to spindles or slow waves. After learning the reach task, reactivations were in fact more closely time-locked and phase-locked (i.e., occurred at a particular phase of the cycle) to fast spindles. Reactivations were also more strongly time-locked and shifted their phase-locking to slow oscillations. Thus, during sleep, neural activation patterns related to the motor task were not only more prevalent after training, but their timing was also refined to coincide with particular neural events that may facilitate memory formation. Since spindles may be involved in synchronizing long-range cortical activity, locking task-specific reactivations to spindles could tie them into neuroplastic changes throughout widespread brain networks supporting consolidation.

At a recent talk on sleep-dependent memory consolidation, the speaker compared the neural reorganization that takes place during memory formation to a house renovation. Just as it’s more comfortable and effective for us to check into a hotel while our house is renovated, learning may be more effective when the brain checks out – into the quietude of sleep – while neural reorganization occurs. This may explain why sleep is so important for learning, yet it doesn’t explain how the brain stores new memories during sleep. Past studies have identified neuronal reactivation, coordinated with spindles and slow waves, as critical for forming declarative memories. Dr. Ramanathan and colleagues’ findings suggest that these mechanisms also occur in the motor cortex to support a radically different form of memory – the kind that helped you learn to ride a bike many years ago.

Clarifying the neural dynamics of sleep-dependent learning holds profound implications not just for those of us hoping to learn to play a new instrument or refine our dance moves. It may also help us better understand the remarkable neuroplasticity that underlies rapid motor learning during early development, and hold potential to promote recovery from motor impairments following brain injury. Dr. Ganguly is optimistic about the possible applications of their findings:

“Motor learning is likely an essential process during rehabilitation. Surprisingly little is known about the role of sleep and replay during recovery. With further study, one could imagine using sleep and offline processing to maximize the learning during rehabilitation.”

References

Ji D, Wilson MA (2007). Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci. 10:100-107. doi: 10.1038/nn1825

Ramanathan DS, Gulati T, Ganguly K (2015). Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation. PLOS Biol. doi: 10.1371/journal.pbio.1002263

Stickgold R (2005). Sleep-dependent memory consolidation. Nature. 437:1272–1278. doi: 10.1038/nature04286

Image credit https://www.flickr.com/photos/echoforsberg/

Any views expressed are those of the author, and do not necessarily reflect those of PLOS.

Emilie Reas received her PhD in Neuroscience from UC San Diego, where she used fMRI to study memory. As a postdoc at UCSD, she currently studies how the brain changes with aging and disease. In addition to her tweets for @PLOSNeuro she is @etreas.