Sleep recalibrates the brain’s memory cells, allowing us to solidify what we’ve learned and use it when next awake, new evidence from mice indicates.
Sleep deprivation, sleep disorders, and sleeping pills can interfere with the process, researchers from the Johns Hopkins University School of Medicine conclude.
“The bottom line is that sleep is not really downtime for the brain.”
“Our findings solidly advance the idea that the mouse and, presumably, the human brain can only store so much information before it needs to recalibrate,” says Graham Diering, a postdoctoral fellow who led the study in the journal Science.
“Without sleep and the recalibration that goes on during sleep, memories are in danger of being lost,” he says.
The researchers looked at a process that had been well studied in lab-grown brain cells but not in living animals, asleep or awake. Known as homeostatic scaling-down, it uniformly weakens synapses in a neural network by a small percentage, leaving their relative strengths intact and allowing learning and memory formation to continue. That prevents brain cells from firing constantly and reaching maximum load. When a neuron maxes out, it loses its capacity to convey information, obstructing memory formation.
To find out if the process occurs in sleeping mammals, Diering focused on areas of the mouse brain responsible for learning and memory: the hippocampus and cortex. He looked for the same changes seen in lab-grown cells during scaling-down.
Results showed a 20 percent drop in receptor protein levels in sleeping mice, indicating an overall weakening of their synapses, compared to mice that were awake.
“That was the first evidence of homeostatic scaling-down in live animals,” says Richard Huganir, professor of neuroscience and senior author of the study. “It suggests that synapses are restructured throughout the mouse brain every 12 hours or so, which is quite remarkable.”
In the sleeping mice, researchers also found, as they expected, significantly higher levels of a protein called “Homer1a,” known to be critical for regulating sleep and wakefulness.
Previous tests with lab-grown neurons had already shown Homer1a playing an important role in the scale-down process. In the new study, researchers found levels of that protein to be 250 percent higher in the synapses of sleeping mice, versus awake mice.
“We think that Homer1a is a traffic cop of sorts,” says Huganir, explaining that the protein evaluates levels of certain neurotransmitters and chemicals to determine when the brain is “quiet enough to begin scaling down.”
The researchers confirmed that sleep is a necessity for this scale-down process that can’t be substituted.
“The bottom line is that sleep is not really downtime for the brain,” Diering says. “It has important work to do then, and we in the developed world are shortchanging ourselves by skipping it.”
Huganir emphasizes that because this study only focused on the hippocampus and cortex, more research is needed on other parts of the brain—and throughout the body—to better understand the necessity of sleep.
The researchers also note the need to look more closely at how drugs known to prevent homeostatic scaling-down, including benzodiazepines and other sedatives or sleep aids, interfere with learning and memory.
Support for the work came from the Canadian Institutes for Health Research, the Johns Hopkins Center for Proteomics Discovery, and the National Institutes of Health.