Lack of sleep wreaks havoc on the brain, making us worse learners and disrupting our memory, among other insults.
Now, a study in mice suggests some of these effects could stem from changes in how brain cells are connected to one another.
In a paper published today in Current Biology, researchers show that just hours of sleep deprivation reduce how many different types of synapses—the places where neurons meet—there are in brain regions associated with learning and memory. The findings hint at a novel way sleep might help keep us sharp, the team says.
The study “is a technical tour de force,” says Marcos Frank, a neuroscientist at Washington State University who was not involved in the work. Still, he and others caution it’s not yet clear whether this result explains sleep deprivation’s unpleasant side effects.
Nerve cells meet and communicate via chemicals across synapses, allowing signals to travel through the nervous system. There are trillions such connections in the human brain, forming and rearranging circuits of neurons that capture and store information. Various theories have tried to invoke these connections to explain the relationship between sleep and memory. One well-known idea from the early 2000s holds that the strength of synapses in the brain decreases when we sleep, and that this is important for conserving energy and prepping the brain for encoding new information the following day.
But such theories often treat synapses as relatively uniform, says Seth Grant, a neuroscientist at the University of Edinburgh. In the past few years, his team and others have found that synapses are surprisingly diverse. They differ not only in the types of chemical, or neurotransmitter, they use to send signals, but in structure and in the composition of proteins present in the neurons surrounding them.
Grant and colleagues previously developed a technique to take a snapshot of this diversity across the brain. First, they engineered mice to produce fluorescent versions of two well-studied proteins made at synapses, PSD95 and SAP102, that hold together lots of other proteins inside neurons. Then, they imaged those mice’s brains using microscopy and classified each synapse into three types depending on whether PSD95, SAP102, or both proteins were present. Combining this with information on the size and structure of each synapse, the concentrations of each protein, and the speed with which proteins are recycled, they came up with a total of 37 distinct subtypes.
In the current study, Grant and his team investigated how this set of synapses—what the researchers dub the “synaptome”—changes with sleep deprivation. To do so, they compared mice that got normal amounts of snoozing with ones kept awake for an extra 6 hours by researchers gently prodding them with a brush or tapping their cages. Brain images showed that although the total number of synapses stayed relatively constant, the diversity of subtypes fell in the sleep-deprived animals, especially in two areas of the brain associated with learning and memory: the cortex and the hippocampus. In particular, the number of synapses that quickly recycled proteins decreased, whereas slow-recycling ones rose.
It’s not clear how sleep deprivation drives this shift, though Grant notes that some previous research has shown a lack of sleep can slow down protein synthesis in cells. Overall, though, the findings suggest sleep plays an important role in preserving synapse diversity in memory-associated areas of the brain, he says—perhaps helping explain why memory takes a hit when we don’t get enough time in bed.
Most previous research hasn’t been able to disentangle differences in synapses at all, let alone show how they change across whole animal brains in response to sleep deprivation, adds Jason Rihel, a neuroscientist at University College London who was not involved in the work. However, he and other researchers say it remains to be seen whether these changes explain why we feel terrible after a night without sleep, or why we need sleep in the first place.
“The biggest difficulty really is to sort through [all these changes in the brain] and figure out what is functionally relevant,” says Dragana Rogulja, a neurobiologist at Harvard Medical School not involved with the new study. Other data in the team’s paper suggest that although the synaptome changes with sleep deprivation, it’s relatively stable across regular sleep-wake cycles, she adds, raising questions about what maintains it across a normal day.
Frank agrees it’s unclear how important the findings are to explaining sleep’s function. “Do I think that preserving synaptic diversity is the answer to the mystery of sleep? Not yet. But I am intrigued at this novel perspective.”
