Team of researchers at the Washington State University's Elson S. Floyd College of Medicine demonstrate the mechanism of astrocytes in regulating sleep.
Examining the cellular mechanism behind sleep could provide potential treatment strategies for sleep disorders and neurological diseases and other conditions associated with troubled sleep. Such conditions include post-traumatic stress disorder, depression, Alzheimer’s Disease, and autism spectrum disorder.
"What we know about sleep has been based largely on neurons," said lead author and postdoctoral research associate Ashley Ingiosi. Neurons, she explained, communicate through electrical signals that can be readily captured through electroencephalography (EEG). Astrocytes--a type of glial cell that interacts with neurons--do not use electrical signals and instead use a process known as calcium signalling to control their activity.
In this present study that was published in September 2020 in the journal Current Biology boosts current understanding of how the brain works during sleep and could move towards solving the mystery of the necessity of sleep. The research suggested that astrocytes in the brain could play key roles in the regulation of sleep as much as neurons.
Astrocytes are known to be support cells in the brain, without any direct involvement in controlling behaviour and neuronal processes. It was only in recent times that these star-shaped cells have gained interested by neuroscientists to take a closer look at its potential role in other processes in the brain. Previous studies have suggested that astrocytes may play a role in sleep, but the technology and tools to study the molecular mechanism was not available until recently.
The research team used a mouse model to identify calcium activity in astrocytes throughout sleep and wake, as well as after sleep deprivation. Using a fluorescent calcium indicator that was imaged via tiny head-mounted microscopes that looked directly into the brains of mice as they moved around and behaved as they normally would. This indicator allowed the team to see calcium-driven fluorescent activity twinkling on and off in astrocytes during sleep and waking behaviours. Their one-of-a-kind methodology using these miniature microscopes allowed the team to conduct the first-ever study of astrocytes' calcium activity in sleep in freely behaving animals.
Looking at astrocytes in the frontal cortex, an area of the brain associated with measurable EEG changes in sleep need, they found that astrocytes' activity changes dynamically across the sleep-wake cycle, as is true for neurons. They also observed the most calcium activity at the beginning of the rest phase--when sleep need is greatest--and the least calcium activity at the end of the test phase, when the need for sleep has dissipated.
The researchers then kept the mice awake for the first six hours of their normal rest phase and watched calcium activity change in parallel with EEG slow wave activity in sleep, a key indicator of sleep need. That is, they found that sleep deprivation caused an increase in astrocyte calcium activity that decreased after mice were allowed to sleep.
To answer whether astrocytes played a part in regulating the need to sleep, the team used mice which did not have the protein known as STIM1 in astrocytes. Lacking this protein reduces the amount available calcium. In these mice, sleep deprivation caused it to not sleep as long or get as sleepy compared to the control mice. These further confirmed previous findings that suggest the astrocytes play an essential role in regulating the need to sleep.
The team also tested whether astrocyte calcium activity is similar to the electrical activity of neurons.
"The findings of our study suggest that we may have been looking in the wrong place for more than 100 years," said senior author and professor of biomedical sciences Marcos Frank. "It provides strong evidence that we should be targeting astrocytes to understand why and how we sleep, as well as for the development of therapies that could help people with sleep disorders and other health conditions that involve abnormal sleep."