Students sometimes pull an all-nighter to prepare for an exam, but research has shown that sleep deprivation is bad for your memory. However, University of Groningen neuroscientist Robbert Havekes, PhD, has discovered that what you learn while being sleep deprived is not necessarily lost; it’s just difficult to recall.
Together with his team, Havekes found a way to make this “hidden knowledge” accessible again days after studying while sleep-deprived using optogenetic approaches and the human-approved asthma drug roflumilast.
The study, published on Dec. 27 in the journal Current Biology, examined whether amnesia as a result of sleep deprivation was a direct result of information loss or merely caused by difficulties retrieving information.
To address this question, Havekes and his team used an optogenetic approach. Using genetic techniques, they caused a light-sensitive protein (channelrhodopsin) to be produced selectively in neurons that are activated during a learning experience. This made it possible to recall a specific experience by shining light on these cells.
First, genetically engineered mice were given a spatial learning task in which they had to learn the location of individual objects, a process that heavily relies on neurons in the hippocampus. The mice then had to perform this same task days later, but this time with one object moved to a novel location.
The mice that were deprived of sleep for a few hours before the first session failed to detect this spatial change, which suggested that they could not recall the original object locations. However, when reintroduced to the task after reactivating the hippocampal neurons that initially stored this information with light, they successfully remembered the original locations.
“This shows that the information was stored in the hippocampus during sleep deprivation, but couldn’t be retrieved without the stimulation,” says Havekes in the release.
The molecular pathway set off during the reactivation is also targeted by the drug roflumilast, which is used by patients with asthma or COPD. Havekes says that when the mice that were trained while being sleep-deprived were given roflumilast just before the second test, they remembered, the same as what happened with the direct stimulation of the neurons.
As roflumilast is already clinically approved for use in humans, and is known to enter the brain, these findings open up avenues to test whether it can be applied to restore access to “lost” memories in humans.
“It might be possible to stimulate the memory accessibility in people with age-induced memory problems or early-stage Alzheimer’s disease with roflumilast,” says Havekes in the release. “And maybe we could reactivate specific memories to make them permanently retrievable again, as we successfully did in mice. If a subject’s neurons are stimulated with the drug while they try and ‘relive’ a memory, or revise information for an exam, this information might be reconsolidated more firmly in the brain. For now, this is all speculation, of course, but time will tell.”
Photo: High magnification image showing part of the mouse hippocampus in which a sparse population of neurons encoding a specific learning event are labeled in red. Neurons that are not activated by the learning event are shown in blue.
Photo credit: Havekes l\Lab / University of Groningen