For something we spend a third of our lives doing, we still understand very little about how sleep works – for example, why some people can sleep soundly through any distraction, while others throwing and turning for hours every night? And why do we all seem to need a different amount of sleep to relax?
For decades, scientists have looked at the behavior of brain neurons to understand the nature of slumber. Now, however, researchers at UC San Francisco have proven that a different type of brain cell that has received much less scrutiny – astrocytes, named for their star-like shape – can have an effect on how long and deep animals sleep. The findings could open up new avenues for exploring sleep disorder therapies and help scientists better understand brain disorders linked to sleep disturbances, such as Alzheimer’s and other dementias, the authors say.
“This is the first example where someone underwent intensive and rapid treatment of astrocytes and showed that it was able to affect sleep,” said Trisha Vaidyanathan, the study’s first author and a graduate student of neuro-science at UCSF. “That sets astrocytes as an active player in sleep. It’s very interesting.”
When we are awake, our brains like Babel of infamous neuronal voices chatter among themselves to allow us to work through the daily activities of life. But when we sleep, the signal sounds of neurons melt into a unified chorus of explosions, called slow-wave action neuroscientists. Recent research has suggested that astrocytes, not just neurons, may help stimulate this inversion.
Comprising about 25 to 30 percent of brain cells, astrocytes are a type of so-called glial cell that covers the brain with innumerable basal tendrils. This cover allows each astrocyte to listen in on tens of thousands of synapses, the sites of communication between neurons. The abundant cells connect to each other through specific channels, which researchers believe could allow astrocytes located throughout the brain to function as a single unified network. The hyperconnected and ubiquitous astrocytes may be able to drive synchronous signals in neurons, as suggested by the new study, published on March 17, 2021, in eLife.
“This could give us new insights not only on sleep but on diseases in which sleep dysregulation is a symptom,” said senior study author Kira Poskanzer, PhD, assistant professor in UCSF’s Department of Biochemistry and Biophysics. “Some diseases may be affecting astrocytes in a way we had never thought of before.”
Poskanzer and her team monitored changes in slow-wave activity in mouse brains while manipulating astrocytes using a drug that can turn the cells on in animals with a genetic engine. Wave-wave activity can be represented in the same way as vibration from seismograph-extracted earthquakes. When the brain awakens, the resulting traces are usually a dense scribble of short, silly movements. But when slow wave activity begins at certain levels of sleep, the signal slows down, slowly bending up and down to create a trail with deep valleys and high peaks. The researchers found that burning of astrocytes led to increased slow-wave activity – and therefore sleep – in the mice.
But the team wanted to study the role of astrocytes in detail, asking how these cells affect them and what aspects of sleep they regulate.
In addition to the specialized pathways that attach to neighboring astrocytes, these cells are filled with receptor molecules that allow them to respond to signals emanating from neurons and other types of cells around them. In the study, the team captured two of these molecules – known as the Gi and Gq receptors – and found that they appeared to control a particular aspect of sleep. Activation of Gq receptors caused animals to sleep longer, but not deeper, according to slow wave measurements, while activating Gi receptors placed in a much deeper thigh without their affecting the entire length of sleep.
“The depth and length of the sides of sleep that often overwhelm and clutter each other even in neurology,” Vaidyanathan said. “But separating these different aspects and how they are managed is going to be important down the line for creating more specific sleep remedies.”
The team also found that astrocyte activity has reached far across the brain: stimulation of astrocytes in one part of the cortex may affect neuronal behavior at a distant location. The researchers are keen to take a closer look at the extent of this effect and continue to study how different astrocytic receptors work together to influence sleep, Poskanzer says.
“What have people been missing because they are bypassing this group of cells?” she was surprised. “The unanswered questions so far in sleep neurobiology – they may not have been answered because we weren’t looking in the right places.”
University of California – San Francisco