A name on the tip of the tongue. That fuzzy feeling when the fact that you learned yesterday has become out of reach. Recalling memories and snippets of information can be infuriating at the best of times, and even more difficult when you’re sleep deprived.
But what if there was a way to reverse that sleep-deprived amnesia and reclaim those fragile memories?
A new study in mice suggests that ‘forgotten’ memories can be retrieved days later, either by activating certain brain cells or with a drug commonly used in humans to treat chronic obstructive pulmonary disease (COPD), a group of diseases affecting the lungs and airways, including emphysema, chronic bronchitis and asthma.
It might sound crazy, but not so much when you think about how memories are somehow chemically encoded in brain cells.
And while the possibility of replicating this in humans is somewhat fanciful, the study reveals a thing or two about the new memories we thought we had lost due to sleepless nights.
Previous research has shown how even brief periods of sleep deprivation affect memory processes, altering protein levels and brain cell structure. But researchers still don’t know whether sleep loss alters how information is stored, making it difficult to access it later, or whether newly formed memories are completely lost when we haven’t slept.
This was the first question University of Groningen neuroscientist Robbert Havekes and colleagues attempted to answer, using mice that were sleep deprived for 6 hours after inspecting a cage with multiple objects.
A few days later, the animals failed to detect that any of the objects had moved to a new position – unless certain neurons in the hippocampus, a thin brain region that stores spatial information and consolidates memories, are activated with the help of light.
This shows that the mice could remember where the original objects were, if the hippocampal neurons encoding that information were given a boost. “The information was, in fact, stored in the brain, but difficult to retrieve,” says Havekes.
The results suggest that memories thought to be “lost” may still exist in an inaccessible state and can be artificially retrieved, at least in mice.
But the technique used to do this, optogenetics, is an experimental approach that requires genetic adjustment (to make cells photosensitive) and as such is still far from being used in humans.
To experiment further in mice with a less invasive approach, the researchers turned to a COPD drug called roflumilast. Among the varied effects of the drug is an increase in levels of a specific cell signaling molecule that decreases when memory is impaired due to sleep loss.
“When we administered roflumilast to trained mice while they were sleep deprived just before the second test, they remembered, just as it did with direct stimulation of neurons,” Havekes says.
Memory-restoring effects with roflumilast were apparent 5 days after initial training, and even longer when the drug and light activation were used.
While the work of Havekes and his team focuses on uncovering the molecular mechanisms of memory and how to restore it, their new research raises age-old questions about how memories – the rich sensory imprints of past experiences that color our lives – are encoded in spongy brain tissue.
For centuries, scientists pondered and then searched for networks of brain cells in which they believed distinct memories were stored. Called engrams, the connectivity and strength of these networks are believed to be essential for storing memories.
Sometimes the existence of engrams as the basic unit of memory has been questioned. But memory engram research has seen a recent resurgence now that scientists have the right tool to manipulate individual populations of brain cells: optogenetics.
Using optogenetics, the researchers induced fear-related “freeze” responses in mice by reactivating a subset of hippocampal neurons that were active during a previous fearful experience.
They also planted a false memory that made mice fear a foot shock in the absence of environmental cues and even boosted memory retrieval in amnesic mice that serve as a model for early Alzheimer’s disease. .
Although this remains the domain of animal studies for now, the long-term goal of this type of research is to understand how information is acquired, stored and recalled in humans – and perhaps, one day , to find a way to help people whose memory is impaired.
“Right now it’s just speculation of course, but time will tell,” Havekes said.
The study was published in current biology.