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Asthma drug brings back “lost” memories

In a study involving mice, scientists used two different techniques — one optogenetic and one pharmacologic — to recover “lost” memories.
Credit: Annelisa Leinbach, sarandy westfall / Unsplash
Key Takeaways
  • Sleep deprivation can cause memory loss.
  • However, is is unclear whether the information that gets “lost” as a result of sleep deprivation is truly gone or just difficult to retrieve. 
  • A recent animal study found that this information can be recovered through two different kinds of treatments.

Losing sleep can have dramatic effects on mental function and cognitive performance. It can, for example, lower alertness, make it harder to concentrate, and lead to worse decision-making.

Sleep is also known to be important for strengthening new memories, and so another consequence of sleep deprivation is amnesia. But whether this memory loss is due to losing the information altogether or because of an inability to access or retrieve it is unclear. 

Research published in the journal Current Biology now shows that the amnesia caused by sleep loss can be reversed, and that a drug used to treat asthma can recover the “lost” information. 

Recovering “lost” memories

Youri Bolsius of the University of Groningen and his colleagues used a state-of-the-art technique called optogenetics to investigate how sleep deprivation affects newly formed memories. They created genetically engineered mice in which a light-sensitive algal protein called channelrhodopsin is expressed in neurons that are activated during memory formation. The researchers then gave the animals a spatial learning task in which they had to learn the location of objects.

The researchers made the mice repeat the test five days later, but this time, one of the objects had been moved. The mice that had been deprived of sleep before retaking the test failed to notice the change, showing that sleep deprivation had interfered with their memories of the objects’ locations.

But those memories weren’t altogether lost. The researchers used pulses of laser light, delivered via optical fibers into the brains of some of the sleep-deprived animals, to reactivate the neurons that had fired during memory location. These mice remembered the original locations of the objects, and noticed the change in location, when they repeated the task. This suggests that sleep deprivation merely interfered with consolidation of the location memories, making the information inaccessible — unless the memory “engram” (that is, the physical trace of the memory) was reactivated.

Earlier work had shown that sleep deprivation lowers levels of the signaling molecule cAMP in the hippocampus, a brain structure which is critical for memory formation, and that drugs that boost cAMP levels prevent the memory deficits induced by sleep loss. Bolsius and his colleagues therefore gave sleep-deprived mice a cAMP-boosting drug called roflumilast, which is prescribed to patients with asthma and chronic obstructive pulmonary disease (COPD), and found that it too restored the animals’ location memories when they retook the test. 

Better treatments for memory disorders

The drug treatment or optogenetic reactivation of the location memories alone restored the “hidden” memories of the objects’ locations up to eight days after learning and sleep deprivation. But combining the two resulted in a longer lasting restoration of the memories.  

Sleep deprivation may lead to memory deficits by preventing “replay” of the network of hippocampal neurons that are activated during memory formation. This would interfere with memory consolidation by preventing strengthening of the synaptic connections within the network. This study shows that neurons in the hippocampus retain the memories nonetheless, albeit in an inaccessible state, but that they can be rescued artificially. 

The researchers hypothesize that roflumilast may promote memory retrieval by an excitatory effect on hippocampal neurons. Their findings could eventually be applied in the clinic to treat memory deficits in conditions such as Alzheimer’s disease.  


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