The Role of Sleep in Engram Reactivation and Memory Consolidation

 Memory formation and retrieval of information are essential for human cognition, but the mechanisms behind these processes are complex and intricate. Advances in neuroscience research highlight the role of engrams, specific ensembles of neurons that are physical substrates of memories. In the early 20th century, Richard Semon proposed that cells that undergo persistent physical and/or chemical changes form an engram. The reactivation of these cells triggers memory retrieval. Recent evidence suggests that sleep is also vital in reactivating these engrams, facilitating memory consolidation associated with subregion-specific biosynthetic changes. Both of these studies support the idea that physical and chemical changes in nervous tissue affect engrams and memory consolidation. 

Dr. Grella talked about Dr. Josselyn and Dr. Tonegawa’s paper, “Memory engrams: Recalling the past and imagining the future,” where they discuss how engrams are cells that undergo persistent chemical or physical changes and reactivation of these cells trigger memory recall. Using modern technologies like optogenetics and chemogenetics, researchers were able to label, silence, and artificially reactivate specific engram cells across multiple brain regions. In mice, loss-of-function studies showed that removing CREB-overexpressing engram neurons could erase memories, while gain-of-function studies demonstrated that artificially stimulating engram cells can induce memory recall without external clues.  The paper also highlighted that engrams are dynamic and are able to shift between active and silent states, yet they aren’t restricted to a single brain region. These findings provide a foundation for understanding how physical and chemical changes in neurons, and nervous tissue, support memory consolidation, extinction, and even create false memories. Building on this work, recent studies have explored the role of sleep in engram reactivation. Their work shows that sleep dependent processes in the hippocampus are associated with subregion specific biosynthetic changes that further support the idea that sleep can help stabilize and consolidate memories.  

In Wang et al.’s paper, “Sleep-dependent engram reactivation during hippocampal memory consolidation associated with subregion-specific biosynthetic changes,” researchers investigate how sleep affects the reactivation of memory-encoding neurons in the hippocampus. Researchers used a mouse model to label the neurons in the dentate gyrus that were active during a fear-learning task. They then examined how these engram cells behaved during post-sleep versus sleep deprivation. Findings showed that sleep promotes the reactivation of engram neurons in the inferior blade of the dentate gyrus. This region of the brain is essential for consolidating contextual fear memories. Sleep deprivation, however, disrupted the reactivation of engrams and suppressed genes associated with neuronal activity. To identify the subregion-specific cellular mechanisms associated with this, they used spatial transcriptomics which revealed that sleep deprivation alters processes like synaptic structure and signaling in hippocampal gene expression. Overall, Wang and other researchers demonstrated that post-learning sleep is crucial for reactivation and stabilization of memory engrams, highlighting the molecular and structural basis of sleep-dependent memory consolidation. 

Therefore, the research done by Dr. Josselyn and Dr. Tonegawa on memory engrams, along with the research done by Wang et al. on sleep-dependent engram reactivation, emphasizes the importance of both neural plasticity and restorative sleep in memory consolidation. Dr. Josselyn and Dr. Tonegawa’s work demonstrates how engrams are the basis of memory storage and retrieval, showing that manipulating these cells can activate and even erase memories. Similarly, Wang and other researchers highlighted that sleep is vital to reactivating these engrams by stabilizing and strengthening memory traces. Together these studies suggest that maintaining a healthy sleep pattern and supporting proper neural function are necessary for long-term memory formation and cognitive performance.   

References

Josselyn, S. A., & Tonegawa, S. (2020). Memory engrams: Recalling the past and imagining the future. Science (New York, N.Y.), 367(6473), eaaw4325. https://doi.org/10.1126/science.aaw4325

Wang, L., Park, L., Wu, W., King, D., Vega-Medina, A., Raven, F., Martinez, J., Ensing, A., McDonald,

K., Yang, Z., Jiang, S., & Aton, S. J. (2024). Sleep-dependent engram reactivation during hippocampal memory consolidation associated with subregion-specific biosynthetic changes. iScience, 27(4), 109408. https://doi.org/10.1016/j.isci.2024.109408