Engrams and Depressive Behaviors - Dana Walker


These two articles created a narrative about memory engram-bearing cells and how they can manipulate fear and depression-related behaviors. Ramirez’s 2013 article focused on creating false memories by fear-conditioning mice in one context while recording which neurons were active, then optically reactivating these neurons in a neutral, novel context. Mice then associated this memory with a fearful context, such as a foot shock, and formed a new fear memory. Ramirez’s 2015 article expanded on this finding. They used this manipulation of memory engram cells to reactivate a positive memory in stressed mice. Reactivation of positive memories, not neutral or negative ones, helped increase struggle time and sucrose consumption, two measures of depressive-like behavior. However, it didn’t affect anxiety-related behavior. It was hypothesized that the BLA-NAc pathway was linked to this effect.
I appreciated the link between the two articles and their potential implications for treating depression and anxiety. However, I have trouble imagining how these results can be tested on or applied to clinical populations. Animal testing is far different from human testing. It would be very difficult to use optogenetics with humans in the same manner they are used with mice. The procedures would have to be altered significantly, as it is likely unethical to alter memories or implant optogenetic equipment in human brains. Furthermore, the idea of “altering memories” has some scary implications and could receive some backlash if applied to humans. Many things could go wrong in the research process, or the end results could be used for the wrong purposes. I believe the field has a long way to go in animal research before it can begin to be considered for clinical phases, and even then, it will likely have to undergo many changes to the protocol. Perhaps the best first step would be to recruit participants with existing mental illnesses such as depression or anxiety. They would think about an existing positive experience (instead of creating one in the lab), which would be labeled for future use. Then, this memory could be reactivated during a depressive episode see if the artificial recollection is enough to improve symptoms.
Alternatively, Positive Psychotherapy (PPT), mentioned as a reference in the 2015 article, could continue to be a clinical alternative for these protocols. PPT, unlike other types of therapy, revolves around positive experiences. Therefore, it could be a valuable, non-invasive way to tell if recalling positive experiences can affect depression- and anxiety-related behavior.

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