Engrams and The Effects on PTSD

 At the beginning of the semester, we had Dr. Stephanie Grella present on the topic of engrams, which are memory traces that all intertwine to provide us with a complete memory. She connected engrams and their effects on consolidating memories, to how behaviors are displayed before and after retrieval. For further background on the topic of engrams, we read the article titled, “Memory engrams: Recalling the past and imagining the future,” by Josselyn and Tonegawa, which goes in depth about engrams and their impact regarding memories. In this article, the researchers were able to manipulate and influence neurons in ways specific to storing and displaying memories. These engrams could be displayed as active, silent, or unavailable. This type of research allowed for the discovery of memory silencing rather than total erasure. It was noted that protein synthesis before or after an experience induces amnesia and blocks cellular consolidation. Cellular consolidation is very important for the retrieval of memories, as it strengthens the synapses to send strong signals regarding a memory. Not only this, but the synapse strength elicits neuronal excitability, and in the context of fear memories, neurons that were noted to have higher excitability were more likely to be distributed through engrams. This can be used to further explain the recall of fear memories and the link between people with PTSD, their associated engrams, and potential treatments.

 

In the article, “Trauma and Remembering: From Neuronal Circuits to Molecules,” by Szabolcs Keri, we can apply the knowledge about engrams mentioned above to those dealing with PTSD (post-traumatic stress disorder). PTSD is an anxiety disorder that emerges from exposure to a specific traumatic event, such as death or injury, which can be associated with certain emotional responses like fear. Although someone with PTSD might not remember many details of the event that led to the trauma, those experiences lead to heightened reactions to neutral contexts. To better understand everything that leads to these reactions, different parts of the brain, like the hippocampus, amygdala, and prefrontal cortex, must be studied due to their overlap. Keri states that the hippocampus, which connects to the cortex, regulates specific details of a dated event by outlining distinct engrams, giving us context like time and place. Meanwhile, the dorsal prefrontal cortex is what controls most of memory retrieval and engram reconstruction, while the amygdala detects threat or danger. In PTSD, this process of pattern separation and incorporation of context fails, which leads to reexperiencing of said trauma through triggers like sounds or smells, due to the emergence of the fear engram.

 

 Through animal studies, PTSD has continued to be studied and treated through psychotherapy with psychedelic substances like MDMA. As a way to treat PTSD, this drug can help with the process of memory reconsolidation and destabilization during retrieval. With the help of proteasomes—which degrade scaffolding proteins—engrams can be modified during their unstable state, which is generally during memory retrieval of the traumatic event. After the modification occurs, the memory is reconsolidated, and the incident is reshaped. This reduced conditioned fear in animals specifically by affecting the serotonin and glutamate systems. In doing so, the psychedelics boosted the synthesis of new proteins, which, as mentioned above, is important for the maintenance and stabilization of engrams through reconsolidation. 

 

Both studies intertwine with Dr. Grella’s presentation regarding memory reconsolidation and destabilization and the effects on engrams. This goes hand in hand with synaptic strength due to the synthesis of proteins and memory retrieval of active, silent, or unavailable engrams, as Dr. Grella explained could lead to dementia and Alzheimer’s. All the research mentioned above allows for many connections to be drawn with modifications in memory traces, which could further help in treating patients with PTSD and dementia.

 

References

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

Kéri, Szabolcs. “Trauma and remembering: From neuronal circuits to molecules.” Life, vol. 12, no. 11, 26 Oct. 2022, p. 1707, https://doi.org/10.3390/life12111707.