“When we used the flow fiber photometry method to look inside the brains of mice, we saw these slow waves of norepinephrine, but we also saw how it works in synchrony with fluctuations in blood volume,” says Hauglund.
Each time norepinephrine levels rose, it caused the blood vessels in the brain to constrict and blood volume to drop. At the same time, the contraction increased the volume of the perivascular spaces surrounding the blood vessels, which were immediately filled with cerebrospinal fluid.
When norepinephrine levels fell, the process worked in reverse: the blood vessels dilated, letting blood in and pushing out cerebrospinal fluid. “What we found was that norepinephrine works a bit like an orchestra conductor and keeps the blood and cerebrospinal fluid moving in synchrony in these slow waves,” says Hauglund.
And because the study was designed to monitor this process in freely moving, undisturbed mice, the team discovered exactly when this was all happening. When mice were awake, noradrenaline levels were much higher, but relatively stable. The team observed the opposite during the REM sleep phase, where norepinephrine levels were consistently low. The oscillatory behavior was exclusively present during the NREM sleep phase.
So the team wanted to check how glymphatic clearance would work if they gave the mice zolpidem, a sleep drug proven to increase NREM sleep time. In theory, zolpidem should have stimulated brain cleansing. But instead it was disabled.
Non-sleeping pills
“When we looked at the mice after we gave them zolpidem, we saw that they all fell asleep very quickly. That was expected: we take zolpidem because it makes it easier for us to sleep,” says Hauglund. “But then we saw that the slow fluctuations in norepinephrine, blood volume and cerebrospinal fluid almost completely stopped.”
