The findings help us better understand why virtually all animals sleep, despite the fact that it leaves us helpless against predators and other threats.

The team, led by members from the University of Tsukuba explains that a certain phase of sleep (rapid eye movement sleep, or REM) gives our brains the opportunity to perform necessary maintenance. This, in turn, ensures that they’re running at peak capacity the rest of the time. The research builds on previous measurements of blood flow in the brain during different phases of sleep and wakefulness, which yielded conflicting results. In this study, the researchers used a technique to directly visualize how red blood cells move through the brain capillaries of sleeping and awake mice, while also measuring electrical activity in the brain.

Housekeeping

“We used a dye to make the brain blood vessels visible under fluorescent light, using a technique known as two-photon microscopy,” says senior author of the study Professor Yu Hayashi. “In this way, we could directly observe the red blood cells in capillaries of the neocortex in non-anesthetized mice.”

“We were surprised by the results. There was a massive flow of red blood cells through the brain capillaries during REM sleep, but no difference between non-REM sleep and the awake state, showing that REM sleep is a unique state”

In order to help elucidate the confusing previous findings around this topic, the authors monitored brain flow rates in different areas of the brain alongside electrical activity. The latter was used to distinguish between different states of awareness (non-REM sleep, REM sleep, full wakefulness). Since we know that the development of certain conditions such as Alzheimer’s — which involve the buildup of waste products in the brain — is associated with reduced blood flow in the brain, the former was used as a rough estimate for maintenance and cleaning processes taking place in the mice’s brains.

The link between the two is that the removal of these waste products involves biochemical processes that eventually culminate in an increased blood flow (as the waste needs to be physically removed) during rest. Disposal of this material doesn’t take place, to the best of our knowledge, during wakefulness; or, at least, not to any extent that we’ve been able to pick up on.

After recording the differences between the three states, the team also disrupted the mice’s sleeping. They report that this resulted in their brains engaging in a “rebound” REM sleeping pattern later in the experiment. This state, which resembles a stronger REM sleeping state, was likely used to compensate for the earlier disruption, the team hypothesizes. This, by itself, suggests that REM sleep has an important role to play in brain functionality.

Later, the team repeated this sleep disruption experiment with mice whose brain A2a receptors were artificially blocked — these are the same receptors that get blocked after you have a cup of coffee, and doing so makes you feel more awake. In these conditions, they saw a much lower increase in blood flow during both REM and rebound-REM sleep. This is a strong indicator “that adenosine A2a receptors may be responsible for at least some of the changes in blood flow in the brain during REM sleep,” says Professor Hayashi.

Judging from these findings, the team says that there may be merit in investigating whether the heightened blood flow seen in brain capillaries during REM sleep facilitates waste removal from brain tissues. This could, in time, lead us towards treatments or preventive measures against conditions such as Alzheimer’s disease. They also point to adenosine A2a receptors as a prime candidate for such treatments, given the observed role of these neurons in modulating blood flow in the brain during REM sleep.

The paper “Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors” has been published in the journal Cell Reports.