Havekes, an associate professor at the Department of Memory and Sleep Neuroscience at the University of Groningen in the Netherlands, and his team have extensively researched how sleep deprivation affects memory processes. “We previously focused on finding ways to support memory processes during an episode of insomnia,” says Havekes. However, in a recent study, his team investigated whether sleep deprivation-induced amnesia is a direct result of information loss or simply due to difficulties in accessing information.
“Sleep deprivation impairs memory processes, but every student knows that an answer that eludes them during an exam can pop up hours later. In this case, the information was actually stored in the brain, but it was simply difficult to retrieve it.”
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To address this question, Havekes and his team used an optogenetic approach: using genetic techniques, they created a light-sensitive protein (channelrhodopsin) to be selectively produced in neurons activated during learning experience. This allowed these cells to remember a particular experience by shining light on them. “In our sleep deprivation studies, we applied this approach to neurons in the hippocampus, where the brain’s spatial information and factual knowledge are stored,” says Havekes.
First, the genetically engineered 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 the same task days later, but this time they moved to a new location with an object. Mice deprived of sleep for several hours before the first session failed to detect this spatial change, indicating that they were unable to remember the original object locations. “However, when we reactivated the hippocampal neurons that originally stored this information with light and re-entrained them, they successfully remembered the original locations,” says Havekes. “This suggests that information is stored in the hippocampus during sleep deprivation but cannot be retrieved without stimulation.”
Asthma medication can treat memory problems
The molecular pathway triggered during reactivation is also targeted by roflumilast, a drug used by patients with asthma or COPD. Havekes: “When we gave roflumilast to the trained mice during sleep deprivation right before the second test, they remembered what happened by direct stimulation of the neurons.” Since roflumilast is already clinically approved for use in humans and is known to enter the brain, these findings open up opportunities to test whether it can be used to restore access to “lost” memories in humans.
For people with memory problems, it’s time to turn back the clock
The fact that there is more information in the brain than we previously expected, and the discovery that these “hidden” memories can be made accessible again—at least in mice—opens up all sorts of exciting possibilities. “In people with age-related memory problems or early-stage Alzheimer’s disease, it may be possible to stimulate memory accessibility with roflumilast,” says Havekes.
“And maybe we can reactivate specific memories so that we can bring them back permanently, as we have done successfully in mice.” If the subject’s neurons are stimulated by the drug while they are ‘reliving’ a memory or revising information for an exam, this information can become more firmly integrated in the brain. ‘It’s all speculation at the moment, but only time will tell.’
Currently, Havekes is not directly involved in such human studies. “My interest is in unraveling the molecular mechanisms underlying all these processes,” he explains. ‘What makes memories accessible or inaccessible? How does roflumilast restore access to these “hidden” memories? As always in science, by asking a question you get many new questions for free.’
Source: Eurekalert
