Yiu et. al. & Ramirez et. al

This week’s articles focused on the concept of memory and ways researchers have attempted to manipulate brain structures associated with memory to understand the mechanisms behind this cognitive ability, particularly with relation to fear.

Yiu et. al. examined a small subset group of neurons in the lateral amygdala known to be involved with fear memory. This experiment used vectors to express various transgenes, specifically excitatory pyramidal neurons. They found that over expressing CREB or dnKCNQ2 in these neurons enhanced fear memory formation. They also found that neurons with higher excitability are preferentially allocated to a fear memory trace. I am curious if, since fear is a primal trait necessary for survival, this is the reason for the recruitment of higher excitability neurons to create a stronger memory. It would be interesting to test other states such as “safety” (remembering where they are safe) and see if there highly excitable neurons are preferentially recruited to encode this safety memory. If preferentially recruiting highly excitable neurons to increase memory strength was unique to fear, it could be a reason why fear memories are persistent and hard to modify. I found this very interesting, particularly when it was shown that enhanced memory was dependent on increased excitability at time of training, not after memory had already been formed, indicating a window in which we could disrupt this preferential recruitment and decrease the strengthening of fear memory.

Ramirez et. al. focused on the dentate gyrus (contextual memory cells) and Ca1 neurons in the hippocampus. After reading the paper, I am not clear why they included Ca1 neurons- is it just because these neurons are known to be involved in memory or were they meant to be something to compare to dentate gyrus neurons? I also thought that as a whole this paper touches upon a very interesting topic, but reading through the text and figures, although a few pages, took me a long time. I found it extremely dense and not as easy to understand as Yiu’s paper.

Ramirez used optogenetic stimulation to induce the memory engram in a context in which a footshock was delivered, pairing the unpleasant footshock with the engram creating a false fear memory. When put back in the “safe” context in which the memory was first created, the mice are now scared because this memory was altered into a “false fear” memory. I thought it was impressive when, after they showed evidence of successfully creating a false memory, they showed it to be context dependent and then applied this to the chamber preference test. I thought seeing Figure 4B with the locomotion traces was impressive and clear in showing that the creating the false memory worked. This experiment when looking at it as a whole was very impressive and slightly unnerving to think that there is potential to create false memories in animals or even humans. When used the right way, this creation of false memories could aid in PTSD treatment, but I think there is a long way to go until this method can be safely and ethically translated to therapeutic use.