Ramirez et. al 2013, 2015

       Ramirez et al. 2013 is a fascinating paper and a novel use of optogenetic activation. By isolating when ChR2 is expressed using the antibiotic doxycycline, the team was able to take what is already an incredibly temporally acute mechanism and further refine that targeting to specific memories in time. Through their experiment they were able to identify that specific neurons are formed in the dentate gyrus in response to specific memories and that reactivation of those memories can induce specific behavioral changes as they relate to those memories. While it seems this original experiment was designed it seems more as a technical paper to prove that such a reactivation was possible, and was designed around an established fear paradigm, it opens incredible opportunities for optogenetic activation of even therapeutic memories, as they explore in their 2015 paper. 

       Following a similar labeling and activation paradigm, the team was able to mark positive memories in the dentate gyrus and, following a chronic stress regiment, were able to rescue depressive symptoms to a level comparable to a simple exposure to said positive experience. Not to mention, in the variety that included regular activation over five days, specific activation of those engrams had a more significant effect than natural exposure to a positive memory which Moreover, a chronic reactivation of said positive engrams has significant effect on neurogenesis. 

       However, there are certain questions raised by their paper. Namely, Ramirez et al. claim that the effects seen by their five-day activation of positive engrams indicates an enduring reversal of stress-induced depressive behaviors, and while they did indicate that there was a significant difference in day-after behaviors as compared to single day activation, a more long term or delayed test of behaviors (say a week later) would be more apt to call the effects enduring as opposed to just the day after. As well, I would be interested to see if the reactivating effects are equally significant if the positive memory is formed post-stress rather than pre-stress.