Awakening Silent Memories: What Alzheimer’s Research Reveals About Engrams

One of the most captivating points from this semester’s talk with Stephanie Grella of the idea that memories in Alzheimer’s disease may not be gone forever, in contrast would be locked away in what are called silent engrams. “An engram is portrayed as a set of neurons that undergoes many chemical or even physical changes during any experience which allows the memory to be stored in the brain.” These engrams are the physical traces of memories that are encoded in the human brain. When a particular situation arises when a patient can’t recall an event, the engram in the brain could still exist–like a file saved on a hard drive, yet hidden behind a forgotten password. This particular perspective reforms memory loss as a problem of access rather than as a complete erasure of the memory. 

A study that includes a very fascinating example in relation of engrams is from Perusini et al. (2017). This specific study explored memory recovery in an Alzheimer’s disease mouse model. The researchers that took part of this research, investigated that mice with Alzheimer’s–like symptoms performed very defectively on memory exams. This has led to the suggestion that mice had “forgotten” the information that they acquired. Yet, when scientists use optogenetics–a technique that uses light to activate the specific neurons in the brain–to restore the dentate gyrus engrams cells that are tied to those specific memories, which lead to the mice suddenly remembered. This overall proposes that memories were stored in the brain, just not easily accessed through the normal route.  

This finding deeply connects to Stephanie Grella’s focus on engram theory and how its fundamental role in such disorders and conditions like Alzheimer's disease. If there are memories that are not truly destroyed yet instead are silenced, then upcoming treatments might aim to “awaken” those silent engrams. As said in the research, engrams cannot be retrieved by the natural way of retrieval but therefore could be recaptured with “direct optogenetic stimulation”. While optogenetics is not currently a practice for humans, the proposition behind it opens the door for other therapeutic strategies. This could include the usage of drugs, stimulation techniques, or other targeted behavioral therapies that could help restore memory retrieval.

Considering memory loss in this particular way, does bring a difference on how we understand late-life illnesses. Instead of analyzing Alzheimer’s as an unbeatable deletion of self, such research like this proposes that the brain retains much more than we realize. The challenge lies in finding such pathways to reconnect the patients with their own memories that shape who they are. Memory may be hidden, yet not fully disappeared. 

References

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

Perusini, J. N., Cuevas, J. S., Shin, J., Yaeger, J. D. W., Goldberg, A. R., Koivisto, M., …Tanaka, K. Z. (2017). Optogenetic reactivation of memory engrams restores memory in mouse models of early Alzheimer’s disease. Nature, 531(7595), 508-512. https://doi.org/10.1038/nature17172