Students sometimes spend an all-nighter to prepare for an exam. However, research has shown that sleep deprivation is bad for memory. Now University of Groningen neuroscientist Robbert Havekes has discovered that what you learn while being sleep deprived isn’t necessarily lost, it’s just hard to remember. He and his team found a way to make this “hidden knowledge” accessible once more within days of studying sleep deprivation using optogenetic approaches and the man-approved asthma drug roflumilast. These results were published on December 27 in the journal Current biology.
Havekes, associate professor of memory and sleep neuroscience at the University of Groningen, the Netherlands, and his team have studied extensively how sleep deprivation affects memory processes. “We previously focused on finding ways to support memory processes during an episode of sleep deprivation,” says Havekes. However, in their latest study, their team examined whether amnesia resulting from sleep deprivation was a direct result of information loss or simply caused by difficulties retrieving information. “Sleep deprivation undermines memory processes, but every student knows that an answer they missed during the exam can show up hours later. In this case, the information was actually stored in the brain, but difficult to retrieve.
Seahorse
To answer this question, Havekes and his team used an optogenetic approach: Using genetic techniques, they induced a light-sensitive protein (canalrhodopsine) to be produced selectively in neurons that are activated during a learning experience. This helped to remember a particular experience by shedding light on these cells. “In our sleep deprivation studies, we applied this approach to neurons in the hippocampus, the area of the brain where spatial information and factual knowledge is stored,” says Havekes.
First, the genetically modified mice were given a spatial learning task in which they had to learn the location of individual objects, a process that relies heavily on neurons in the hippocampus. The mice then had to perform this same task a few days later, but this time with an object moved to a new location. Mice that were sleep-deprived for a few hours before the first session failed to detect this spatial change, suggesting that they cannot remember the original locations of objects. “However, when we reintroduced them to the task following reactivating the hippocampal neurons that initially stored this information with light, they were able to remember the original locations,” says Havekes. “This shows that information was stored in the hippocampus during sleep deprivation, but might not be retrieved without the stimulation. »
Memory issues
The molecular pathway triggered during reactivation is also targeted by the drug roflumilast, used by patients with asthma or COPD. Havekes: “When we gave trained mice roflumilast while they were sleep deprived just before the second test, they remembered, just as it did with direct stimulation of neurons. As roflumilast is already clinically approved for use in humans and known to enter the brain, these findings open avenues to test whether it can be applied to restore access to ‘lost’ memories. in man.
The discovery that more information is present in the brain than we expected, and that these “hidden” memories can be made accessible once more – at least in mice – opens up all sorts of exciting possibilities. “It might be possible to boost memory accessibility in people with age-related memory problems or early-stage Alzheimer’s disease with roflumilast,” says Havekes. “And perhaps we might reactivate specific memories to make them permanently retrievable once more, as we have successfully done in mice. If a subject’s neurons are stimulated by the drug as they try to “relive” a memory or revise information for an exam, that information might be reconsolidated more firmly in the brain. “At the moment this is all speculation of course, but time will tell. »
At present, Havekes is not directly involved in such studies in humans. “My interest lies in uncovering the molecular mechanisms that underlie all these processes,” he explains. ‘What makes memories accessible or inaccessible? How does roflumilast restore access to these “hidden” memories? As always with science, by tackling a question you get many new questions for free.
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Materials provided by University of Groningen. Note: Content may be edited for style and length.
