Researchers successfully bring mice's memory back with an asthma medicine

The finding that these "hidden" memories can be accessed once more, at least in mice, throws up a world of intriguing possibilities.
Nergis Firtina
A lab mouse.
A lab mouse.


Neuroscientist Robbert Havekes and his team at the University of Groningen found that learning while sleep-deprived does not result in memory loss; rather, it is more difficult to recall.

Havekes and the team used optogenetic techniques and the human-approved asthma medicine roflumilast to find a means to make this "hidden knowledge" accessible once more days after researching while sleep-deprived.

"We previously focused on finding ways to support memory processes during a sleep deprivation episode," says Havekes. On the other hand, in Havekes’ most recent research, his team looked at whether amnesia brought on by lack of sleep was a direct result of information loss or merely brought on by issues retrieving information, according to the release.

"Sleep deprivation undermines memory presses, but every student knows that an answer that eluded them during the exam might pop up hours afterward. In that case, the information was, in fact, stored in the brain, but just difficult to retrieve."

Optogenetic approach

Havekes and his team adopted an optogenetic strategy in which they genetically engineered neurons that are stimulated during a learning experience to manufacture a light-sensitive protein selectively. By placing a light on these cells, it was feasible to recollect a specific experience.

"In our sleep deprivation studies, we applied this approach to neurons in the hippocampus, the area in the brain where spatial information and factual knowledge are stored," said Havekes.

Researchers successfully bring mice's memory back with an asthma medicine
High magnification image showing part of the mouse hippocampus.

Targeted by the drug roflumilast

The medication roflumilast, which is taken by people with asthma or COPD, also targets the biochemical pathway triggered during the reactivation.

"When we gave mice that were trained while being sleep-deprived roflumilast just before the second test, they remembered, exactly as happened with the direct stimulation of the neurons," Havekes said.

These discoveries bring up opportunities to explore if roflumilast can be used to give individuals access to lost memories, as it is already clinically licensed for use in humans and is known to penetrate the brain.

The finding that the brain stores more information than we previously thought and that these "hidden" memories can be accessed once more, at least in mice, throws up a world of intriguing possibilities.

The study was published in Current Biology on December 27

Study abstract:

It is well established that sleep deprivation after learning impairs hippocampal memory processes and can cause amnesia. It is unknown, however, whether sleep deprivation leads to the loss of information or merely the suboptimal storage of information that is difficult to retrieve. Here, we show that hippocampal object-location memories formed under sleep deprivation conditions can be successfully retrieved multiple days following training, using optogenetic dentate gyrus (DG) memory engram activation or treatment with the clinically approved phosphodiesterase 4 (PDE4) inhibitor roflumilast. Moreover, the combination of optogenetic DG memory engram activation and roflumilast treatment, 2 days following training and sleep deprivation, made the memory more persistently accessible for retrieval even several days later (i.e., without further optogenetic or pharmacological manipulation). Altogether, our studies in mice demonstrate that sleep deprivation does not necessarily cause memory loss but instead leads to the suboptimal storage of information that cannot be retrieved without drug treatment or optogenetic stimulation. Furthermore, our findings suggest that object-location memories, consolidated under sleep deprivation conditions and thought to be lost, can be made accessible again several days after the learning and sleep deprivation episode using the clinically approved PDE4 inhibitor roflumilast.

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