week 3

I love the progression of these two papers.  You can really see how the 2013 paper explains a novel discovery, the possibility of creating a false memory in mice, and then see this used in a more clinical context in the 2015 paper regarding how activating a previous positive memory can help ameliorate depressive behaviors. Regarding the 2013 paper, I thought their method of testing a false fear memory was really innovative. It took me a couple tries to fully understand it, but it seems like a great way to test a false memory. I liked that they also controlled for generalization and for effects of mCherry itself by using a ChR2-EYFP group to show the same results. It was also really interesting that the false memory was only successful when reactivating DG neurons, not CA1 neurons. I think this speaks to the incredible specificity of the hippocampus and how memories are encoded and recalled. Later on, they also show that recalling a genuine or false fear memory leads to activation of neurons in the basolateral amygdala and central amygdala. This is interesting because it speaks to the difficulty humans have in correctly recalling highly emotional memories, or how memories can often be encoded falsely during highly emotional events. I also enjoyed the short commentary on another paper that was able to create a synthetic memory. I am curious how these authors tested whether a synthetic memory was created in an animal model.

            The 2015 Ramirez paper lends itself better to discussion. This study used a 10 day chronic immobilization stress (CIS) paradigm to induce depressive and anxious behaviors in mice, as tested by the TST, SPT, OFT and EPMT tests. I really liked that this paper separated the depressive and anxious symptoms. They show that optically reactivating cells in the DG associated with a positive memory can ameliorate depressive symptoms in mice induced by the CIS paradigm. Interestingly, activating positive memory engrams had no effect on the anxiety-related behaviors of the mice. This ties into the Bessa paper, which showed that neurogenesis was not required to ameliorate depressive symptoms in mice induced by chronic mild stress, but neurogenesis was required to affect anxiety-related behaviors. I think this points to a new way of thinking about depression and anxiety, that perhaps these disorders have different pathologies, and although they may overlap or exist concurrently clinically, that they have different effects in research and should be investigated separately. My other favorite point of this paper was that they showed that exposing the stressed mice to a positive experience did not have the same rescuing effect as reactivating the DG cells associated with the positive memory. This is super interesting, because it hints to the human phenomenon – you can’t just do fun things with a depressed person and cure them. I thought it was really cool that this translated over to the animal model, and it really shows that treatments for depression must manipulate on the cellular and molecular plane to be effective.