"We used a dye to make the brain blood vessels visible under fluorescent light, using a technique known as two-photon microscopy," said 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-anaesthetised mice," added Professor Hayashi.
The researchers also measured electrical activity in the brain to identify REM sleep, non-REM sleep, and wakefulness and looked for differences in blood flow between these phases.
"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," explained Professor Hayashi.
The research team then disrupted the mice's sleep, resulting in "rebound" REM sleep -- a stronger form of REM sleep to compensate for the earlier disruption.
Blood flow in the brain was further increased during rebound REM sleep, suggesting an association between blood flow and REM sleep strength.
However, when the researchers repeated the same experiments in mice without adenosine A2a receptors (the receptors whose blockade makes you feel more awake after drinking coffee), there was less of an increase in blood flow during REM sleep, even during rebound REM sleep.
"These results suggest that adenosine A2a receptors may be responsible for at least some of the changes in blood flow in the brain during REM sleep," said Professor Hayashi.
Given that reduced blood flow in the brain and decreased REM sleep are correlated with the development of Alzheimer's disease, which involves the buildup of waste products in the brain, it may be interesting to address whether increased blood flow in the brain capillaries during REM sleep is important for waste removal from the brain.
This study lays the preliminary groundwork for future investigations into the role of adenosine A2a receptors in this process, which could ultimately lead to the development of new treatments for conditions such as Alzheimer's disease.