Summary: New mouse research shows that sleep deprivation can hide memories rather than erase them, and that those hidden memories can be recovered with drugs already approved for human use. The study presented at the FENS Forum 2024 reports that roflumilast, an anti-inflammatory medication used for asthma and chronic obstructive pulmonary disease (COPD), restored social memories, while vardenafil, a drug used for erectile dysfunction, recovered spatial memories.
These results point to promising avenues for treating memory impairment caused by lack of sleep. While the work is preclinical and was conducted in mice, it establishes a foundation for further research into therapies that could one day help people recover memories made inaccessible by sleep loss.
Key facts:
- Sleep deprivation in mice makes certain social and spatial memories inaccessible rather than destroying them.
- Researchers were able to restore these hidden memories using roflumilast for social memory and vardenafil for spatial memory.
- The findings suggest potential strategies for developing treatments for sleep-related memory problems in humans, though clinical translation will require further work.
Source: FENS
Overview
Research presented by Dr. Robbert Havekes and colleagues from the University of Groningen at the Federation of European Neuroscience Societies (FENS) Forum 2024 examined how a single episode of sleep deprivation affects memory consolidation and retrieval in mice. Prior studies have shown sleep loss impairs memory, but this team investigated whether those memories were lost or simply rendered inaccessible.
The team tested two types of memory: social recognition and spatial object-location memory. For social memory tests, mice were offered a choice between interacting with an unfamiliar mouse or a familiar cage-mate. Normally, mice show an initial preference for the novel mouse and, by the next day, treat both animals as familiar. If the mice were sleep-deprived after the initial encounter, however, they behaved as if they had not met the other mouse before—indicating impaired recall of the social encounter.
For spatial memory, mice were trained to recognize the locations of objects. A brief period of sleep deprivation after training prevented recall of the objects’ original positions, so the mice failed to detect when an object was moved during testing.
How hidden memories were recovered
To demonstrate that memories remained encoded but inaccessible, the researchers first used optogenetic engram technology. This method identifies and tags neurons that form a specific memory (a memory engram) and allows those neurons to be reactivated with light. Reactivating the engram restored the mice’s ability to recall the social encounter, supporting the idea that memory traces persisted despite sleep deprivation.
Building on this proof of concept, the researchers tested two FDA-approved drugs. Treating sleep-deprived mice with roflumilast—an anti-inflammatory drug used in COPD—restored social memory recall. Treating mice with vardenafil—commonly prescribed for erectile dysfunction—restored spatial object-location memory. These pharmacological recoveries occurred days after the original learning and the sleep deprivation episode.
Dr. Havekes said these results identify molecular pathways in the hippocampus and other brain regions that can be targeted to make memories retrievable after sleep loss. He emphasized that while the findings are encouraging, translating them into human treatments will require careful clinical investigation. The work presented at FENS Forum 2024 was supported by the Air Force Office of Scientific Research (AFOSR) and involved PhD researchers Adithya Sarma and Camilla Paraciani.
Implications and next steps
The study suggests a distinction between memory encoding and accessibility: sleep deprivation can block retrieval without erasing the underlying engram. If similar mechanisms operate in humans, targeted neuropharmacology could one day restore access to memories made inaccessible by sleep loss. The research team is collaborating with other groups to begin human studies, with the aim of better understanding which processes determine whether a memory remains accessible or becomes hidden.
Professor Richard Roche, chair of the FENS Forum communication committee, noted that the work highlights potential for recovering social and spatial memories in people, but cautioned that moving from mice to human treatments will take time and substantial additional research.
About this sleep, memory, and neuropharmacology research news
Author: Kerry Noble
Source: FENS
Contact: Kerry Noble – FENS
Image: The image is credited to Neuroscience News
Original research presentation: Findings presented at FENS Forum 2024