The first week of this semester, we had the pleasure of listening to Stephanie Grella present her research on the formation and retrieval of memories involving the engram. Her studies aimed to identify engram cells and discover how information is stored and retrieved in the engram, as well as learn how the structure of an engram can affect the quality of memory functions, how engrams interact with one another, and how engrams can change over time.
To find answers to these questions, the results of observational studies, loss-of-function studies, gain-of-function studies, and mimicry experiments were compiled and analyzed. Most, if not all, of these studies look at the memory function of mice. One finding that I found interesting is the synaptic plasticity and strengthening of the engram during fear conditioning experiments. Some characteristics of these engrams include increased dendritic spine density and neuronal excitability. Both of these characteristics correlate with functioning memory retrieval and storage. Another interesting finding is the effects of damaging engrams and the evidence of silent engrams. Damaged engrams may result in memories that can no longer be retrieved, but silent engrams are engrams that contain memories that can only be retrieved through artificial means. In the study discussed, researchers were able to induce amnesia in mice by disrupting protein synthesis and discovered that silent engram cells showed less of an increase in synaptic strength and dendritic spine density than other engrams. A decrease in synaptic activity and dendritic spine density is related to the silencing of an engram, decreasing its overall function. In an experiment where researchers gave rats an LTP-like optogenetic stimulation, it was discovered that the stimulation impaired their memory function and silenced specific engrams. However, it was also found that the same stimulation could allow memories from these silenced engrams to be retrieved. I think that a lot of the findings discussed by Grella have many implications for future possible cures, treatments, and preventions of neurodegenerative diseases, including Dementia and Alzheimer's. I believe these findings have great potential to influence new research regarding these diseases, and most likely already have. Now that researchers better understand engrams and how they relate to memory function and decline, the next step could be applying these findings to medical research.
The research that Stephanie Grella presented to our class made me wonder what further research on engrams might have been done recently. A research article by Freddy Jeanneteau investigates the effect that stress has on the risk of Alzheimer’s Dementia. In his article, Jeanneteau asks the question of whether deconstructed engrams can be rebuilt to restore memory functions. In this article, the many biochemical effects of stress and stress-related hormones and their similarities to mechanisms of underlying neurodegenerative diseases are discussed in detail. One thing about Jeanneteau’s research that stood out most to me is the effect that chronic stress has on engram functions. Experiments similar to those discussed in Grella’s research (administering experimental LTP to mice to induce amnesia) are correlated in this article to chronic stress and the body’s release of glucocorticoid, a stress response hormone. It is also noted that dendritic spine clustering, a characteristic related to functioning engrams in Grella’s research, is impaired in Alzheimer’s Dementia. Jeanneteau explains that this might happen because of the destruction that chronic stress hormones cause to the mechanisms of neuron and synapse maintenance. The maintenance of these synapses between engrams could potentially retrieve a pathway of connected neurons and retrieve lost memories. However, plaques like amyloid-β prevent these networks from excitability and are usually found near silent neurons and engrams. This research takes the findings from Grella’s presentation and applies them to a medical context. I believe that the findings discussed by Grella and Jeanneteau could potentially be developed further into effective solutions to diseases like Alzheimer’s Dementia. Learning the biological mechanisms of memory and memory decline is imperative to developing methods of prevention, treatment, and possibly a cure.
References
Jeanneteau, F. (2023). *Stress and the risk of Alzheimer's dementia: Can deconstructed engrams be rebuilt?* *Journal of Neuroendocrinology*. Advance online publication. [https://doi.org/10.1111/jne.13235](https://doi.org/10.1111/jne.13235)
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](https://doi.org/10.1126/science.aaw4325)
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