Sleep helps recalibrate brain cells responsible for learning and memory, mice study shows

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NEW YORK, Feb 3: Studying mice, scientists at Johns Hopkins have fortified evidence that a key purpose of sleep is to recalibrate the brain cells responsible for learning and memory so the animals can “solidify” lessons learned and use them when they awaken — in the case of nocturnal mice, the next evening.

The researchers, all of the Johns Hopkins University School of Medicine, also report they have discovered several important molecules that govern the recalibration process, as well as evidence that sleep deprivation, sleep disorders and sleeping pills can interfere with the process.

“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, Ph.D., the postdoctoral fellow who led the study. “Without sleep and the recalibration that goes on during sleep, memories are in danger of being lost.”

A summary of their study appears online in the journal Science on Feb. 3.

Diering explains that current scientific understanding of learning suggests that information is “contained” in synapses, the connections among neurons through which they communicate.

On the “sending side” of a synapse, signaling molecules called neurotransmitters are released by a brain cell as it “fires”; on the “receiving side,” those molecules are captured by receptor proteins, which pass the “message” along. If a cell receives enough input through its synapses, it fires off its own neurotransmitters.

More specifically, experiments in animals have shown that the synapses on the receiving neuron can be toggled by adding or removing receptor proteins, thereby strengthening or weakening them and allowing the receiving neuron to receive more or less input from nearby signaling neurons.

Scientists believe memories are encoded through these synaptic changes. But there’s a hitch in this thinking, Diering says, because while mice and other mammals are awake, the synapses throughout its brain tend to be strengthened, not weakened, pushing the system toward its maximum load. When neurons are “maxed out” and constantly firing, they lose their capacity to convey information, stymying learning and memory.

One possible reason that neurons don’t usually max out is a process that has been well-studied in lab-grown neurons but not in living animals, asleep or awake. Known as homeostatic scaling down, it is a process that uniformly weakens synapses in a neural network by a small percentage, leaving their relative strengths intact and allowing learning and memory formation to continue.

To find out if the process does occur in sleeping mammals, Diering focused on the areas of the mouse brain responsible for learning and memory: the hippocampus and the cortex. He purified proteins from receiving synapses in sleeping and awake mice, looking 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, Ph.D., professor of neuroscience, director of the Department of Neuroscience and lead author of the study. “It suggests that synapses are restructured throughout the mouse brain every 12 hours or so, which is quite remarkable.”

To learn specifically which molecules were responsible for the phenomenon, the team turned to a protein called Homer1a, discovered in 1997 by Paul Worley, M.D., professor of neuroscience, who was also part of the team conducting the new study. Studies showed that Homer1a — named for the ancient Greek author and the scientific “odyssey” required to identify it — is important for the regulation of sleep and wakefulness, and for homeostatic scaling down in lab-grown neurons.

Repeating his previous analysis of synaptic proteins, Diering indeed found much higher levels of Homer1a — 250 percent more — in the synapses of sleeping mice than awake mice. And in genetically engineered mice missing Homer1a, the previous decrease of synaptic receptor proteins associated with sleep was no longer present.

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