Week 3: Memory Engrams

In 2012, Ramirez et al. made an astounding discovery when they were successful in using optogenetic techniques to manipulate memory engram-bearing hippocampal neurons for the recollection of artificially implanted memories. Using this first experiment as a precursor, they proposed exploiting this model as a potential alleviation for stress response and depressive-like behavior three years later. Both studies used transgenic c-fos-tTA mice injected with an AAV encoding ChR2-mCherry to specifically label cells in the dentate gyrus, which were then reactivated during a behavioral fear conditioning paradigm in different contexts to control for memory. After exposure to context “A” and a subsequent foot shock paired with electrical light pulses while in context “B”, mice demonstrated freezing response when placed back in context “A”. The data elicits the idea that fear can be activated regardless of whether the aversive foot shock was provided in that context, hence the induction of false memories if encoded in the same engram. The second publication especially stood out to me, being that the overall results indicate that chronic stimulation of DG cells associated with positive memory leads to significant stress-induced behaviors as well as an increase in neurogenesis.

After reading both papers, I also watched Ramirez’s TED Talk (2017) where he explained how he derived his motivation behind the experiments. It brought me to thinking what would happen if we could indeed erase traumatic and stressful memories in humans as a “cure” for anxiety and mood related disorders. The translational implications of this is tremendous, being that this means a potential alternative to traditional corrective methods such as antidepressants. Neuroscientists have toyed with the idea of altering and destroying memories for sometime now, especially with the radical electroconvulsive therapy. An optogenetic alternative poses a (much) more specific and direct target of engram disruption, which could be quite useful in a clinical setting. And although it is accompanied by ethical and moral dilemmas—for instance, would “deleting” a traumatic event prevent our past from informing our present selves—it achieves plasticity at a faster rate than any medication would. The data is exciting, but we certainly still have ways to make before reconfiguring the mnemonic memory circuit becomes the standard for treating maladaptive behavior.