Memory acquisition and re-activation under the contexts of fear and depression- Sierra Smith

One thing I noticed while reading both of these papers identifying effects of reactivating either fear memories of positive memories and their relationship to fear responses and depression phenotype is that I have already become a more skeptical and thorough reader of publications through taking this seminar course. Initially, in the Ramirez et al. 2015 paper, I found myself wondering about the validity of their initial positive memory elicitor to label DG cells, a female mouse, in terms of whether they are causing the effect they set out to use. I am wondering if what they observed when the group witnessed a behavioral rescue to non-stressed levels in escape behaviors on the TST after reactivation of the labeled positive memory cells under stress induced conditions wasn't related to a mating response as opposed to simulating a positive memory. Is it possible that these mice had a memory of a mate available reactivated, causing these mice to want to seek out the female to breed with and try to escape the TST instead of having more desire to escape under a true alleviation of depression-like symptoms?
I noticed an interesting finding also in Ramirez et al. 2015 related to their use of a glutamate receptor antagonist in the nucleus accumbans. Having just presented on the Tye paper from last week, the results from their glutamate receptor antagonist experiment in the nucleus accumbans was fresh in my mind where they witnessed increase escape related behaviors where that group had been expecting to observe an amelioration in escape related behavior after blocking glutamate signaling. This seems to contrast with the Ramirez finding that blocking glutamate activity in the nucleus accumbans prevented the rescuing effects of the positive experience on escape behavior on the same test, the TST. Although it's difficult to truly compare these studies, this stood out to me as a red flag I'd like to discuss in more detail in class to sort out what these differential effects could be stemming from.
Overall, it is an incredible finding that Ramirez, in his 2013 paper, was able to create an entirely new fear memory at all under a context in which no fear conditioning actually occurred. This finding is what allowed him to later use the very same technique, but this time activating a positive memory instead of a fear memory, to study depression and alleviation of depressive symptoms in a mouse model. I was particularly interested in the discussion in the 2013 paper related to competitive conditioning, and how this may have impeded their experiment when the memory induced in context A cut down on the initial fear response from conditioning in context B upon re-exposure. I wonder if this has anything to do with extinguishing the fear response over time, whereas repeated exposure to a conditioned stimulus can cause the stimulus to elicit less of a response. This is also something I'd like to discuss in class and why it may or may not be confounding the results, as this concept of competitive conditioning is proposed by Ramirez.

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