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Paper Response #3: Memory Engrams

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WEEK 4: Feb. 3 Papers (Ramirez et. al, 2013 and 2015)

Both of Ramirez’s papers examine the effects of optogenetically reactivating dentate gyrus (DG) memory engram cells, but in different contexts and for very different purposes. 

In the 2013 paper, Ramirez and his team identified DG engram cells in mice that were activated during exploration of a neutral environment, and reactivated them during fear conditioning in a different context to create a new, false memory in the hippocampus. As a result, the mice learned to associate the neutral environment with the negatively salient stimulus (foot shock) they experienced during fear conditioning, despite never having been exposed to said stimulus in the neutral environment. A false memory had now been created in the mice’s hippocampi of experiencing pain and fear in a context where they had not experienced these things, thus combining two separate memories and eliciting an observable behavioral fear response (freezing). 

This study moves us closer to understanding the mechanisms by which false memories are created in humans, an area of great interest in both psychiatry and the fields of criminal justice and law enforcement, as false memories in witness statements are not uncommon but can be highly problematic and complicate investigations. However, as mice cannot verbally communicate with us, we are left with many questions about the shape these artificially created memories take. Do mice really “remember” these experiences that never happened in a conscious way, or are their behavioral fear responses merely the result of neuronal impulses with no emotional association or mental representation beyond self-preservation and instinct? Additionally, this paper raises questions about the practical implications of creating new memories beyond simply furthering our understanding of how false memories work. If the spread of misinformation is already an issue in our society today, how much worse would it be if others could generate false memories in our brains at will? Could this technique be modified to be used medically, perhaps to help patients with dementia and related disorders recover memories? The ethical ramifications of all of this would be complex to navigate.

Conversely, in the 2015 paper, Ramirez and his team reversed depression-related behaviors in mice that had been induced by stress by reactivating DG engram cells that had previously been active during a positive experience. This also rescued neurogenesis. Importantly, the beneficial effects of reactivating engram cells associated with a positive memory were mediated by the DG-Basolateral Amygdala (BLA)-Nucleus Accumbens (NAcc) pathway, and inhibiting the DG-Medial Prefrontal Cortex (mPFC)-NAcc pathway did not interfere with this rescue process. 

The results of the 2015 study have more clear real-world applications, namely as a potential treatment for depression that has the benefit of being fast-acting. It is clear to see that Ramirez built on his 2013 research on memory engram cells and further developed it while exploring a completely new angle. It would be interesting to see what other memory-related avenues of research could be opened by examining and manipulating DG engram cells further, like for example intentionally erasing memories instead of creating new ones. 

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