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Week 3: Ramirez 2013 and 2015

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 These research papers, Ramirez 2013 and 2015, focus on memory encoding through the use of optogenetics in the hippocampus and how this can affect anxiolytic and depressive-like behaviors in mice. 

Specifically, the first paper introduced this technique of stimulating certain hippocampal cells in order to create false memories and tested its effectiveness using context-based fear memory. Ramirez et al created the false memories in mice that were experiencing implemented doxycycline withdrawal. They introduced these mice them into a novel context A and traced which cells in the hippocampus became activated using ChR2-mCherry. Then, the team used optogenetic techniques to stimulate these same cells encoding context A while delivering a fear conditioning foot shock known as context B. Finally, they tested the effects of this fear conditioning by exposing the same mice either again to context A or to a new context C and observed the results. The mice that were placed back into context A displayed a significantly higher amount of freezing behavior than those placed into context C and control groups. This research paper was extremely important because it revealed a breakthrough technique for implementing false fear memories into mice. 

            In the second paper, Ramirez 2015, this optogenetic fear-based memory technique was tested to see if it could reduce depressive behavior in mice by activating positive memories stored in the dentate gyrus. The researchers used mice experiencing doxycycline withdrawal and measured the activity in their dentate gyrus with ChR2-mCherry, once again. The mice then were subjected to a period of chronic immobilization stress and examined for depressive behaviors with tests such as with the open field test, tail suppression test, and sucrose preference tests -  all of which we discussed in depth during class. The results confirmed that the stressed group showed increased depressive behaviors. Using optogenetics, the team then activated the cells in the dentate gyrus correlating to a positive experience and the results showed a rescue of the non-depressive behaviors the mice originally exhibited. In other words, activating a positive memory in the mice reversed the effects of stress-induced behavior. The paper goes on to explore why this is happening and what the neural mechanisms driving this effect may be, including projections of the dentate gyrus to the basal ganglia and nucleus accumbens.

I found these papers interesting in that the first described the use of an exciting new method, while the second used that exact method to uncover important and applicable information relating fear-memories and positive associates to the amelioration of depressive behavior. Although it may be far in the future until we have a way to induce false memories in humans or use this method to treat depression, the second study provides promising results that may spark an effort to do further research on this topic. In general, I think there is a lot to learn in regards to the creation of false memories in humans and how it is affected by trauma, depression, and external input (i.e. in police interrogations and witness statements). The link between depression and memory is something that I have not read much about besides in this paper and further investigation could reveal more of the nuances of depression and the differences in how individual’s experience it.

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