Week 4 - Memory Engrams

Both papers this week examine the memory trace originating in the amygdala during fear conditioning. Han et al examined the memory trace and how to eradicate it. Essentially, the researchers found that neurons in the Lateral Amygdala (LA) express CREB to create a fear memory, or the hypothesized memory trace. When those specific cells where selectively killed through dipheria toxin (DT), the mice appeared to forget all fear conditioning for a sustained period of time. The group used controls of mice that were injected with the toxin and had apoptosis, but not on the specific CREB expressing neurons, and the mice still retained fear memory showing the CREB neurons were the ones with the memory trace. Yiu et al furthers Han’s lab research by examining what predisposes a neuron to participant in the memory trace. They find that neuronal excitability immediately before the memory formation is the ultimate factor in determining which neurons express CREB (and are therefore part of the memory trace). 

For Han, while I think the group did many tests and chose a fitting control group to prove the efficacy of their hypothesis and results, I wish they had explored more of the hippocampus’s role. I understand that due to funding and lab limitations, that just may not have been an option, but if memory is a topic, the hippocampus is usually discussed. The lateral amygdala makes sense to study because it is fear conditioning and has functional connections with the hippocampus, but it cannot be the epitome of the whole memory trace. It evidentially plays a very critical role in fear memories as shown through this experiment, but I wonder if the CREB expressing neurons in the LA called on neurons in the hippocampus for the contextual memory itself? Yiu et al briefly looks at the hippocampus, but just in terms of neuron excitability, not its specific functional role in the memory trace. I would be interested in the hippocampus’s role in the memory trace beyond fear conditioning and more in the context of episodic details. To test this, researchers could set up another experiment like last week’s paper and put the mice in different settings, fear condition them, any see if you could specifically ablate cells in the hippocampus and/or amygdala and what effect that has. Additionally, I would be curious to see other forms of fear conditioning besides the auditory fear conditioning used, just to ensure any experimental results are not specific to auditory conditioning.       

Lastly, as Yiu et al’s group touches on in terms of artificially activating the CREB neurons as a cue to retrieve the memory, I think it would be interesting to see how many of these CREB neurons are required to keep the memory trace intact/recall it. For some individuals with ischemic damage to their hippocampal neurons, they are able to retain certain memories as long as the whole hippocampus is not destroyed. While the amygdala is very different, I wonder if it could be the same – if only parts of the neurons are required to recall the memory. For example, if only half of the CREB activated neurons are destroyed, could the fear response still be retained?