Researchers induce the memory-boosting benefits of sleep in parts of the awake brain

A recent study suggests that triggering specific, sleep-like brain wave patterns in awake mice can provide the brain with the restorative benefits usually only gained by actually falling asleep. The findings indicate that the physical need for sleep, as well as the memory-boosting effects of a good night’s rest, might be replicated without the animal ever losing consciousness. This research was recently published in the journal Nature Neuroscience.

Sleep is a biological necessity for all mammals. It serves to reset the brain and body after a long period of wakefulness. When an animal is awake, it learns, moves, and experiences new things in its environment. All of this waking activity causes the microscopic connections between brain cells, known as synapses, to grow stronger and more numerous.

If synapses constantly grow stronger day after day without ever resetting, the brain would become physically overloaded, consume too much energy, and lose its ability to process new information. Deep sleep provides evidence of a massive resetting process across the brain. During non-rapid eye movement sleep, which makes up about eighty percent of total sleep in adults, the junctions between neurons that make memories are evaluated.

During this sleep phase, the brain protects important connections for long-term storage, prunes those that are less necessary, and makes space for new ones. The brain also experiences highly synchronized electrical activity. Millions of neurons will fire electrical signals all at once, creating what scientists call an “on” period. Immediately following this burst, the cells will collectively go silent, which is known as an “off” period.

This rhythmic switching back and forth creates slow brain waves that can be recorded by sensors. Scientists track this slow-wave activity to measure how badly an animal needs sleep. The longer an animal stays awake, the more intense the slow-wave activity will be once it finally falls asleep. As the animal rests over several hours, this activity gradually decreases, indicating that the biological need for sleep has been satisfied.

A research team from the University of Wisconsin-Madison, including Kort Driessen, Fabio Squarcio, Giulio Tononi, and Chiara Cirelli, wanted to test a specific question about these brain waves. The researchers previously showed that both rats and humans can exhibit sporadic, local slow-wave brain activity while awake if they are sleep-deprived. While those brief dips into sleep-like activity might not be enough to provide benefits, the team reasoned that a longer, more systematic version of this activity might allow part of the brain to rest while the animal remains active.

“What we’re essentially doing is forcing sleep in a local region of the brain. While that part is solidifying memories and restoring learning capacity, other parts stay aware/vigilant and connected to the environment,” said Chiara Cirelli, a professor of psychiatry at the University of Wisconsin-Madison. “Dolphins do something similar, sleeping with only one brain hemisphere at a time.”

To test this idea, the researchers used a technique called optogenetics. This method involves genetically modifying specific brain cells so they can be controlled by flashes of light. The scientists implanted tiny light-emitting devices, alongside electrical recording sensors, into the brains of adult mice. These implants were placed on both the left and right sides of the brain.

This design allowed the team to manipulate the neural networks on one side while using the opposite, untouched side as a natural control for comparison. In the first set of experiments, the researchers worked with nineteen genetically modified mice. They kept the animals awake for five hours by continually introducing new objects into their cages.

During the final thirty minutes of this sleep deprivation period, the scientists used light pulses to force the neurons on one side of the brain into rhythmic on and off periods. They tailored the light flashes to mimic the exact timing and duration of natural deep sleep waves. During this entire process, the mice remained awake and behaved normally, moving around their cages without interruption.

After the thirty minutes of light stimulation, the sleep deprivation ended, and the mice were allowed to fall asleep naturally. The researchers closely monitored the brain activity during the first hour of this recovery sleep. The side of the brain that received the artificial on and off periods showed significantly less slow-wave activity than the untreated side. Additionally, the neurons on the treated side fired with much less synchronization.

In sleep science, less synchronization provides evidence that the biological pressure to sleep has been successfully relieved in that specific area. The authors then asked if simply lowering the overall activity of the brain without a rhythm would have the same effect. Some scientists had suggested that an overall reduction in neuronal firing might be the mechanism needed to recover from the cellular fatigue caused by staying awake.

The researchers ran a second experiment with seven different genetically modified mice. Instead of creating a rhythmic on and off pattern, the scientists used a continuous beam of light to quiet the brain cells, broadly reducing their overall firing rates. When these mice were allowed to sleep, both sides of their brains showed the same high need for rest. This finding suggests that the specific rhythm of turning neurons on and off, rather than a general reduction in brain activity, is required to fulfill the restorative functions of sleep.

Next, the team looked at the physical connections between brain cells. They analyzed molecular markers of synaptic strength in twenty-four mice. These mice were split into three groups of eight based on their specific genetic modifications, including a control group. After keeping the mice awake and applying the rhythmic light stimulation to one side of the brain, the scientists immediately collected brain tissue without letting the animals sleep.

In the brain tissue, the researchers measured the levels of specific proteins that help transmit signals between neurons. They found significantly fewer of these receptors on the synapses of the light-stimulated side. This reduction mirrors the natural weakening of cellular connections that occurs during normal deep sleep. This specific weakening process tends to prevent the brain’s networks from becoming overloaded with information.

Finally, the researchers tested whether this artificial brain rhythm could rescue memory after a period of sleep deprivation. They used a behavioral test of tactile memory, an ability that relies heavily on rest. The team used thirty mice for a memory test involving floor textures. On the first day, the mice explored an enclosed chamber with two identical floor textures for fifteen minutes.

Afterward, the animals were divided into three testing groups. Nine mice were allowed to return to their cages and sleep normally. Thirteen mice were kept awake for an hour. Eight mice were kept awake for an hour but received the artificial on and off brain stimulation during that time.

The following day, the mice were placed back into the testing chamber. This time, the chamber featured one familiar floor texture and one entirely new texture. Because mice naturally prefer to explore novel environments, a well-rested mouse will spend more time investigating the new floor.

The mice that slept normally recognized the old floor and spent most of their time investigating the new one. The mice that were simply kept awake failed to recognize the familiar floor, spending equal time on both sides. However, the mice that received the rhythmic light stimulation while awake performed just as well as the well-rested mice.

While these findings are deeply informative, they require proper contextualization to avoid broad misunderstandings. Casual readers might misinterpret the study to mean that humans or animals could entirely replace a full night of sleep with localized brain stimulation. The authors note that completely disconnecting from the environment, as happens during natural sleep, is likely still necessary for the brain to process memories on a large, system-wide scale. The localized stimulation in this study only affected specific, targeted regions of the sensory and motor cortex, not the entire brain.

Another limitation is that the methods used in this study are highly invasive. Optogenetics requires the genetic modification of brain cells and the surgical implantation of hardware into the skull. Because of this, this exact technique cannot be tested on human subjects. The researchers also pointed out that artificial brain waves, depending on the specific type of cells targeted, can sometimes exhibit reversed electrical polarities compared to naturally occurring sleep waves.

Future research will likely focus on how these local rest periods affect the overall health of the brain over much longer stretches of time. Cirelli aims to learn whether similar effects could be replicated in humans using less invasive technologies, like transcranial stimulation. Understanding the exact mechanics of these on and off periods could eventually guide new treatments for severe sleep disorders or age-related memory issues.

“This research further decodes why we sleep and how we learn, which brings us a step closer to understanding how to better prevent and treat cognitive decline,” said Amy Bany Adams, acting director of the National Institute of Neurological Disorders and Stroke, which funded the research.

The study, “Induction of cortical on/off periods in awake mice fulfills sleep functions,” was authored by Kort Driessen, Fabio Squarcio, Giulio Tononi, and Chiara Cirelli.