Ramirez 2013&2015

I thoroughly enjoyed reading the 2013 Ramirez paper on the creation of a false memory using context-specific DG granule cells and viral marking using ChR2-mCherry (although on a small note, I’m not familiar with c-fos and I’m wondering about the significance of the transgene and how it relates to the experiment, if at all). I thought their paradigm was extremely clever and their self-assessment was logical. Other students such as June and Matthew G have expressed confusion about figures 3A and 3B because of the seemingly contradictory statements regarding the potential for interfering CS contexts, but the graph in 3A supports this statement by showing that upon re-entry to genuinely fearful context B, mice who had received stimulation to generate falsely fearful context A initially showed a significantly lower fear response than those mice that did not receive light stimulation to generate falsely fearful context A. Now, although this particular data point could be interpreted in other ways (general fatigue after chronic stress, perhaps?) I do agree with the experimenters in thinking of it as a downgraded initial fearful response because of the sharp increase in stimulated rats once the light was turned on again in the context in question (B’). To me, this lessens the likelihood that the difference in initial fear response is due to fatigue – the potential to reactivate a strong fear response is clearly demonstrated. Thus, the fearful memory of context B is downgraded by the falsely fearful memory of context A, but when the light is turned on and the memories are additive, a robust response is observed once more.

As reflected in this particular response, I was much more interested in Ramirez’s 2013 paper than his 2015 paper – for no other reason than my skepticism of his model of depressive stress behavior. His findings that recall of positive memory contexts using the same techniques as in his 2013 paper is absolutely stunning. However, as he and his co-authors note at the end of the 2013 paper, “However, human studies performed using behavioral and functional magnetic resonance imaging techniques have not been able to delineate the hippocampal subregions and circuits that are responsible for the generated false memories.” So again, while the results are extremely fascinating, I’m not convinced that his model is translatable – the findings are only significant in the sense of an interesting general neuroscience breakthrough.