ANN ARBOR – Sleep, a behaviour vital for both physical and mental health, has long puzzled scientists. Now, researchers at the University of Michigan (U-M) may have a new description for one of sleep’s enduring mysteries: how the different stages of sleep impact memory.

Most living organisms that sleep cycle through periods of low brain activity followed by periods of high activity, including vivid dreams. During this high-activity stage, rapid eye movement, or REM, occurs.

With few exceptions, such as those with narcolepsy or individuals experiencing sleep deprivation, this non-REM to REM sleep cycle is common throughout the animal kingdom.

“Evolutionarily, it’s so preserved and so ubiquitous across species. That means there’s probably something really significant about that particular order of sleep.”

Despite the universality of this phenomenon, the biological function has remained elusive.But now, U-M researchers led by Sara Aton and Michal Zochowski have developed a theory based on experiments in mice and computer modeling of brain circuitry.

The theory suggests that non-REM sleep helps memories grow “taller and stronger,” while REM sleep “prunes” them, keeping them distinct and preventing them from overlapping, according to a U-M release.

“It only works if you have this sequence.If you go in reverse and have REM first, it prunes everything away. Then no memory is left,” Aton said. “In the proper sequence, you reinforce things that need to be reinforced. Then REM comes in to prune back the overlapping portions of unrelated memories.”

The researchers observed the effect of sleep on memory in mice through simple conditioning experiments. Michal Zochowski suggests this could have implications for humans as well.

“Let’s say you have three meetings in a day. We certainly know that you’ll remember these meetings better after a good night’s sleep,” Zochowski said. “Now,it appears that during non-REM sleep,you’re strengthening your memory of each meeting. But you also need to remember who said what and during which meeting. What REM does is keep that separate.”

“Now we have to prove that the model is associated with reality.”

The findings were published in PLoS Computational Biology.The research was supported by the National Science foundation, the Chan zuckerberg Initiative, and the National Institutes of Health.

Cycles and Circuits

Aton’s team monitored the brains of mice to identify which parts of the hippocampus were active during different sleep phases after a conditioning scenario.

The mice were moved to a new environment and given a mild shock. A control group experienced no shock. Researchers then compared brain activity during REM and non-REM sleep cycles to see how memories were formed.

Because current techniques cannot pinpoint individual neurons encoding specific memories, the team used computer modeling. Zochowski’s group developed a model that treats new memories as changes in neuron activity, modulated by acetylcholine.

“We can actually simulate and pinpoint which neurons are being activated by a learning event,” Aton said. “We can model that and we can model changes that happen with respect to acetylcholine as an animal goes through the different stages of sleep.”

The model incorporates excitatory neurons,which stimulate neighbors,and inhibitory neurons,which dampen activity. By combining these dynamics with real-world data on brain activity and acetylcholine levels, the model revealed previously inaccessible insights.

The researchers acknowledge that their circuit model is a simplified portrayal of the brain and that the experiments tested simple memory scenarios.The theory may evolve as it undergoes more complex testing.

“What we have now is a study that says, ‘Look, this is what could be happening,'” zochowski said. “Now we have to prove that the model is associated with reality.”