Week 3: Ramirez 2013 and Ramirez 2015

I thought the “Creating a False Memory in the Hippocampus” was particularly dense and difficult to read. Perhaps due to my inexperience in the field, there were a few elements to the paper that created confusion. First and foremost, I was confused as to why the researchers presented the distinct context (context D) in their search to identify whether memory recall could be induced for a false fear memory by light reactivation of the corresponding engram in the DG. While I understood the basis of the experiment, I was confused as to why they used the context D rather than context C. To my understanding, context C was the novel context. This was something that stuck out to me and left me confused.

Additionally, in Figure 3A, I would have thought that ChR2-mCherry light group would have shown the competing vs. additive interaction between the false memory and the genuine memory. As indicated in their paper, “it is possible that the light-activated DG cells encoding context A interfered with the acquisition or expression of the genuine fear memory for context B”. It would seem, based on that understanding, that the group which had the context A labeled cells activated by the light during fear conditioning in context B would have the most interference and therefore “competition” between the two fear memories. Could it be that that no light group’s context A labeled cells, which had no fear associated with them, had a mitigating effect on the fear response evoked by context B? While a small part of the paper, the issue of false memories interfering with real memories (in a fear based paradigm) is of particular interest to me.

In regards to the 2015 Ramirez paper, I thought it was incredibly interesting that their data showed that chronic stimulation of positive experience DG engram cells elicits an “enduring reversal of stress-induced behavioral abnormalities”. Their hypothesis as to normalization of VTA firing rates harkened back to the Tye et al. paper from last week, showing that normalizing bursting rates of VTA neurons could ameliorate behaviors induced by chronic stress. This seems to give some weight to the Tye paper.