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Post 3: Ramirez et al. 2013 & 2015

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In the first article published by Ramirez and colleagues in 2013, they present a technique that they used to create and evoke a false fear memory using optogenetic stimulation of hippocampal DG cells. In the second article (2015), Ramirez and colleagues use optogenetic stimulation of DG cells to revive a past positive memory and show that this can be used to alleviate depressive behaviors.

The 2013 article demonstrated the utility of the false memory creation technique in fear memory experiments and the specificity of the dentate gyrus in this mechanism. The authors found that light-activated false memories were qualitatively equal to real memories, could be additive to or competitive with genuine memories, and that stimulation to the DG - but not CA1 neurons - can evoke a false memory. This work set the stage for using optogenetic stimulation to reactivate positive memories in different contexts in their 2015 work.

In the 2015 study, Ramirez and colleagues optogenetics to reactivate a positive memory in mice that have undergone chronic immobilization stress to induce anxiety- and depression-related symptoms. The animals were tested on two anxiety measures (open field test (OFT) and elevated plus maze test (EPMT)) and two depression measures (tail suspension test (TST) and sucrose preference test (SPT)). Their findings suggested that reactivating a positive memory can rescue stress-induced depressive behaviors, but not anxious behaviors. Chronically repeated reactivation of a positive memory can create a longer lasting reversal in depressive behaviors and increase neurogenesis activity, but repeatedly exposing a stressed mouse to a positive experience is not enough to alleviate depressive behaviors.

Ramirez and colleagues' first study in 2013 allowed them to introduce a technique, demonstrate its ability to manipulate memories, and let others validate it as well. This made a way for their work in 2015 to be accepted and taken at its value. The value of emotional memories in disorders like depression, anxiety, and PTSD is potentially life-changing. Being able to manipulate these memories and examine the pathways that underlie mood disorders in the way that Ramirez and colleagues did in their 2015 study could be the basis of developing new, more effective treatments for depression and understanding the ways that current effective treatments work to alleviate depressive symptoms.

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