Week 3

This week, I thoroughly enjoyed reading the work from the Ramirez lab. In comparison to our previous readings, I liked reading two papers from the same experimenter, which I believe built upon each other and contributed to a bigger picture.

I began with the 2013 study, on the optogenetic activation of specific memory cells in sync with a conditioned fear stimulus. When I began the paper, I was a bit skeptical of the experimenter's ability to activate certain cells that would undoubtedly recall a specific memory. However, after the confirmation that Context A activated cells were repeatedly activated during Context A exposure, and there was little overlap between Context A and Context C activation, I was more convinced. This is just one example of the thoroughness that Ramirez maintained throughout the paper. By testing other areas (the CA1) and testing preference (conditioned place-avoidance test), the hypothesis that activation of DG neurons can be linked with a conditioned fear response is convincing. However, I did have a couple reservations about the conclusions, especially in regards to the freezing times. With the higher freezing occurrences, does this definitely prove that the animal is recalling the foot shock? Additionally, the percentage of freezing for these fear-induced memories while in Context A is around 30%. While this is statistically significant from the other groups with background freezing occurrences, it still occurs in less than a majority of animals. The argument could have been strengthened if Ramirez included the freezing percentages for complete control animals who receive a foot shock in Context X and are returned to Context X. In fact, Ramirez does indicate at the end of the paper that there was reduced expression in both false and genuine fear memories compared with normal fear conditioning. Additionally, it would be interesting to see whether, when placed back in Context B, there was an increase in freezing as well. In other words, if the animal also associated the fear with the original context in which it was given, in addition to the recalled context. *This might be what Figure 3A is depicting but I wasn't entirely sure what that procedure was designed for.

The 2015 article was extremely interesting and while developing on the principles of the 2013 paper, brought up interesting ideas that could I believe eventually be integrated into therapy. My biggest question while reading this paper was if the activation of the DG genuinely brought up "positive memories" or if it just induced neurogenesis due to activation. After further reading though, I realized that when compared with activation of "neutral memories", there was a statistically significant difference. Overall, I have little criticism for this paper and I appreciated the thoroughness of testing various circuits involved in depression. While it was disappointing to see a lack of change in stress and anxiety, this agrees with papers from Week 1 indicating that stress and anxiety may be resolved in very different ways then depressive symptoms. While it may be a stretch, this paper could lead to the idea that hypnosis (or intense visualization and remembering) of positive memories could lead to a decrease in one's depressive behaviors.