Foregoing a good night’s sleep may wreck the brain’s ability to make new memories.
A new study from Johns Hopkins University School of Medicine demonstrated that a key purpose of sleep is to recalibrate the brain cells responsible for learning and memory, solidifying lessons learned for when the sleeper is awake.
Using a mouse model, the researchers 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.
Graham Diering, Ph.D., the postdoctoral fellow who led the study, explained that the results from the mouse study can be used to make determinations about the human 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,” he said in a statement. “Without sleep and the recalibration that goes on during sleep, memories are in danger of being lost.”
According to Diering, 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, which enables those molecules to be captured by receptor proteins, which pass the message along.
If a cell receives enough input through its synapses, it fires off its own neurotransmitters.
Experiments in animals have shown that the synapses on the receiving neuron can be toggled by adding or removing receptor proteins, which thereby strengthen or weaken them and allow the receiving neuron to receive more or less input from nearby signaling neurons.
It is believed that memories are encoded through these synaptic changes, but Diering said that while mice and other mammals are awake the synapses throughout the brain tend to be strengthened, not weakened, pushing the system toward its maximum load.
When the neurons are maxed out and constantly firing, they lose their capacity to convey information, stymying learning and memory.
One of the reasons that neurons don’t max out is a process known as homeostatic scaling down, where synapses are uniformly weakened in a neural network by a small percentage, which leaves their relative strengths intact and allow learning and memory formation to continue.
Diering focused on the areas of the mouse brain responsible for learning and memory by purifying proteins from receiving synapses in sleeping and awake mice, looking for the same changes seen in lab-grown cells during scaling down.
This resulted in 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,” Richard Huganir, Ph.D., professor of neuroscience, director of the Department of Neuroscience and lead author of the study said in a statement. “It suggests that synapses are restructured throughout the mouse brain every 12 hours or so, which is quite remarkable.”
Diering found 250 percent more of Homer1a—a protein important for the regulation of sleep and wakefulness and for homeostatic scaling down in lab-grown neurons—in the synapses of sleeping mice than awake mice.
The researchers looked to neurotransmitter noradrenaline, which drives the brain to arousal and wakefulness, to sort of how the protein senses when the mice are sleeping or awake.
To test whether the location of Homer1a was related to sleep, the research team kept the mice awake for four extra hours by placing them in an unfamiliar cage. Some of the mice were then given two and a half hours of recovery sleep.
The levels of Homer1a in the receiving synapse were much higher in the sleep-deprived mice than in those that got the recovery sleep.
“We think that Homer1a is a traffic cop of sorts,” Huganir said. “It evaluates the levels of noradrenaline and adenosine to determine when the brain is sufficiently quiet to begin scaling down.”
For the final test the researchers tested the mice’s ability to learn without scaling down by placing individual mice in an unfamiliar arena and giving them a mild electrical shock, either as they woke up or right before they went to sleep. Some mice also then received a drug to prevent scaling down.
When an undrugged mouse received a shock just before sleep its brain went through the scaling-down process and formed an association between the arena and the shock, while when placed in that same arena those mice spent about 25 percent of their time motionless, in fear of another shock.
When placed in a different, unfamiliar arena, they only froze about 9 percent of the time.
“We think that the memory of the shock was stronger in the drugged mice because their synapses couldn’t undergo scaling down, but all kinds of other memories also remained strong, so the mice were confused and couldn’t easily distinguish the two arenas,” Diering said. “This demonstrates why ‘sleeping on it’ can actually clarify your ideas.
“The bottom line is that sleep is not really downtime for the brain,” he added. “It has important work to do then and we in the developed world are shortchanging ourselves by skimping on it.”
The study was published in Science.