We Might Finally Know How The Brain Refreshes Itself at Night
As you lay your head down to sleep tonight and dream all things weird and wonderful, scientists think your brain is going through a gentle rinse cycle, washing away a day's worth of toxic by-products in preparation for a new day of thinking ahead.
But the mechanisms behind this neurological cleansing system have yet to be described in detail.
Now researchers from the University of Copenhagen have applied a suite of technologies to map the subtle rise and fall of neurotransmitters, blood volume, and spinal fluid in mice as they go about their day.
The findings don't only help us understand better how the brain refreshes itself at night, they also reveal a surpise downside to common sleep drugs like Ambien.
Colorfully described as the brain's 'sewage network', the biological plumbing technically referred to as the glymphatic system is an anatomical novelty in many respects, having only been identified in mice a little over a decade ago.
Ongoing investigations have since mapped the network in human brains, revealing the glymphatic system draws spinal fluid deep into the brain's interior to carry away materials that risk causing damage in high concentrations. Some of these waste products are linked to Alzheimer's disease.
This 'sewage removal' also helps balance water levels across the brain, facilitates the presentation of potentially dangerous agents of disease to the immune system, and even helps deliver supplies of fuel to where it's needed most.
Studies on how the brain ejects material into the waste removal system to be rhythmically washed away for removal suggest brain wave patterns orchestrated collectively by neurons coordinate the process. Yet they typically rely on anesthetized animal models, leaving questions on how a naturally-occurring sleep-wake cycle manages its glymphatic system.
What's more, some have begun to challenge some of the fundamental assumptions of the process, such as whether it's truly a sleep-dependent exercise at all.
"The motivation for this research was to better understand what drives glymphatic flow during sleep, and the insights from this study have broad implications for understanding the components of restorative sleep," says Maiken Nedergaard, senior author and co-director of the University of Rochester's Center for Translational Neuromedicine.
To trace the brain-washing process back to its physiological roots, researchers developed a new method of fiber optic implants which allowed them to record the dynamics of fluids through the brains of mice as the animals ran relatively free about their cages.
By tagging the neurotransmitter norepinephrine and using the fibre optic implant to activate light-sensitive genes engineered into the animal's brain tissues, the team could monitor and experiment on fluctuations in waste removal while the mice were asleep and while they were awake.
The researchers' work supported earlier studies showing norepinephrine caused blood vessels to contract rhythmically over pulses lasting around 50 seconds, followed by a subtle oscillation in blood volume throughout the brain.
This relationship between neurotransmitter fluctuations and changing blood volumes was far more pronounced while the mice were in a non-dreaming sleep state than awake or in a dream-phase.
Furthermore, they demonstrated experimentally these pulsations did, in fact, drive the glymphatic system into penetrating further into the brain, affirming the role deep sleep plays in clearing out the garbage left by a day's hard thinking.
"These findings, combined with what we know about the glymphatic system, paint the whole picture of the dynamics inside the brain, and these slow waves, micro-arousals, and the norepinephrine were the missing link," says the study's first author, neuroscientist Natalie Hauglund.
Not just any old sleep will do, either. Inspired by claims that sleep-aid pharmaceuticals like Zolpidem – sold as Ambien – can alter sleep phases, the research team tested what impact, if any, the drug had on the cleaning process, finding it reduced the oscillations and impeded the ability for cerebrospinal fluid to work its way into the brain's depths.
Translating the work to humans will rely on further experiments, though it's a safe bet our brains behave in relatively similar ways.
This doesn't mean sleep medication doesn't have its place, though knowing it comes with a potential cost to our ability to hose out each day's neurological scraps might weigh into future decisions on the best ways to keep our brains healthy.
This research was published in Cell.
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