Week 4: Han and Yiu

Reading this week’s papers left me with a sense of satisfaction because of how well thought-out I found both experiments to be. At first, I was more inclined to appreciate Han et. al’s paper because of how clean the work was. In my opinion, ablating the neurons with increased CREB was a great method for proving the necessity of these neurons in fear memory stability. I also appreciated their use of cntrl-cre to ablate a similar amount of neurons as the CREB-cre, proving that general neuron loss was not responsible for the memory loss. Thinking about the clinical implications of this finding is fascinating. If selectively destroying neurons in the LA can erase a fear memory, there may be a potential treatment here for people with PTSD. However, I am skeptical about this because destroying these neurons with increased CREB may hinder human function in ways that we cannot yet predict, so further research would be necessary to evaluate the lasting effects of this experiment.

The Yiu et. al paper expanded on these findings by asking if CREB overexpressing neurons are recruited to a memory trace due to being more excitable than their neighbors. I appreciated that they used a variety of methods to do this, including DREADDS and optogenetics. I was a bit put off by the fact that they were not able to determine excitability in vivo, and had to resort to ex vivo manipulations. Regardless, both papers have raised a lot of questions about neurons with increased CREB expression. I would love to know if any other types of memories are preferentially stored in CREB neurons. I would also love to know what the significance/use of neurons with low CREB expression are. What would ablating those neurons do to otherwise healthy subjects? Are CREB overexpressing neurons responsible for more than just auditory fear memories? If so, could selective stimulation of CREB overexpressing neurons during various contextual exposures, similar to last week’s papers, be enough to create a false fear memory? This exciting research manages to both satisfy my curiosities and create new ones.