Penn biologists work to prevent sleepiness-induced memory lapses

With 35 percent of Americans reporting fewer than seven hours of sleep each night, sleep deprivation is a nationwide public health concern. Failing to get enough sleep can have significant mental and physical effects, among them, impaired memory formation.

In a new study out this week in Science Signaling, a team from Penn was able to prevent this sleepiness-induced memory dip in mice. Their work identified a molecular pathway required to produce proteins involved in the creation and maintenance of memories.

“While this study isn’t immediately translatable to humans, it does lay the groundwork for the identification of the proteins targeted by sleep deprivation,” says Ted Abel, the Brush Family Professor of Biology in the School of Arts & Sciences and senior author of the paper. “This study also provides a hint about the function of sleep to drive protein synthesis and the strengthening of memories.”

The research team confirmed that sleep-deprived mice had reduced levels of newly formed proteins in their hippocampus, a region of the brain known to be important for memory formation. The researchers then zeroed in on a molecular pathway they suspected to be involved in this protein formation, known as the mTOR pathway. Examining sleep-deprived mice, they found that levels of proteins in this pathway were reduced compared to rested mice.

Adding back one of these proteins using a viral vector delivered to hippocampal neurons not only restored protein synthesis in the hippocampi of sleep-deprived mice, but also prevented the mice from experiencing memory deficits. Mice that received injections of the experimental vector performed as well on a test of spatial memory as did rested mice.

“We were able to essentially block the effect of sleep deprivation on memory by manipulating the expression of one gene in the hippocampus,” says Jennifer C. Tudor, a postdoctoral researcher in the Department of Biology and the study’s lead author. “It turns out that the pathway involved is also incredibly important for cell metabolism, so the connection to energy regulation is potentially very interesting.”

Because the mTOR pathway is involved in sensing the body’s energy balance, the findings could shed light on how sleep affects not only cognition, but metabolism, as well.

Mouse memory