Current Biology: Asthma pills allow mice to recover "lost" memories!

Students sometimes drive night trains
for exams.
However, studies have shown that lack of sleep is harmful
to memory.
Now, Robbert Havekes, a neuroscientist at the University of Groningen, has found that what you learn when you're sleep-deprived isn't necessarily lost, it's just hard to recall
.

Together with his team, using optogenetic methods and the human-approved asthma drug roflumilast, after studying for a few days in sleep-deprived conditions, he found a way to get this "hidden knowledge" back to use
.
The findings were published in the journal Current Biology
.

Havekes, an associate professor of memory and sleep neuroscience at the University of Groningen in the Netherlands, and his team have extensively studied how sleep deprivation affects memory processes
.
"We previously focused on finding ways to
support the memory process during sleep deprivation," Havekes said.
However, in his latest study, his team investigated whether sleep-deprived amnesia is a direct result of information loss or simply the result
of difficulty retrieving information.

Sleep deprivation disrupts the memory process, but every student knows that answers they don't find on the exam can pop up hours later
.
In this case, the information is actually stored in the brain, it's just hard to retrieve
.
”

Neurons in the hippocampus

To solve this problem, Havekes and his team used an optogenetic approach: using genetic techniques, they selectively produced a light-sensitive protein (channel rhodopsin)
in neurons that were activated during learning.
This makes it possible
to recall specific experiences by irradiating these cells.
"In our sleep deprivation study, we applied this approach to neurons in the hippocampus, an area of the brain that stores spatial information and factual knowledge," Havekes said
.

First, the genetically engineered mice were given a spatial learning task in which they had to learn the position of individual objects, a process that relied heavily on neurons
in the hippocampus.
After a few days, the mice had to perform the same task, but this time, an object was moved to a new location
.
Mice that were deprived of sleep for several hours before the first session failed to detect this spatial change, suggesting that they were unable to recall the location of the
original object.

"However, when we reactivated the hippocampal neurons that originally stored this information with light and let them perform the task again, they did succeed in remembering the initial location," Havekes said
.
"This suggests that during sleep deprivation, information is stored in the hippocampus but cannot be extracted
without stimulation.
"

Memory issues

The molecular pathways triggered during reactivation are also targeted by the drug roflumilast, which is used in patients with
asthma or COPD.

"When we gave the trained mice sleep-deprived roflumilast before the second test, their memory was like
when neurons were directly stimulated," Havekes said.
Because Roflumilast has been clinically approved for use in humans and is known to have access to the brain, the findings open avenues
for testing whether it can be used to recover "lost" memories in humans.

There is more information in the brain than we previously thought, and the discovery that these "hidden" memories can be retrieved again — at least in mice — opens up all sorts of exciting possibilities
.

"It is possible to stimulate memory accessibility with roflumilast in people with age-sexual memory problems or early Alzheimer's disease," Havekes said
.
"Maybe we can reactivate specific memories so that they are permanently restored again, as we have successfully done in mice
.
"

If subjects are stimulated by medication while trying to "revisit" a memory or review information for an exam, the information may re-consolidate
more firmly in the brain.
"At the moment, of course, it's all speculation, but time will tell
.
"

Currently, Havekes is not directly involved in such human studies
.
"I'm interested in revealing the molecular mechanisms behind all these processes, what makes memory accessible?" How does Roflumilast restore access to these "hidden" memories? Science is always like this, solve one problem, you get a lot of new problems
for free.
”