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Paper Response #4: Han 2009 and Yiu 2014


WEEK 5: Feb. 10 Papers (Han et. al, Yiu et. al)

This week’s papers examined the neurons and neuronal mechanisms involved in various memory processes such as memory formation, expression, and erasure. Han’s 2009 paper argued that a specific subset of neurons in the Lateral Amygdala (LA) containing a higher concentration of cyclic adenosine monophosphate response element–binding protein (CREB) are significantly more likely to be activated by expression of a fear memory after fear memory training, and that removing these neurons results in loss of the fear memory, indicating their importance in the memory trace. On the other hand, Yiu’s 2014 paper showed that allocation of neurons to the memory trace is mediated by relative neuronal excitability prior to training, and that increased neuronal excitability also enhances memory formation. 

Upon reading both papers it was clear to see that Yiu’s research built off of Han’s, going above and beyond Han’s findings to examine why exactly LA neurons with increased levels of CREB are preferentially recruited into the memory trace. What Yiu found was that Han’s version of events was too simplistic and did not show the full picture. While it is true that neurons with increased CREB levels are recruited into the memory trace at higher rates, this is not because of the presence of CREB itself, but because CREB increases neuronal excitability. Yiu showed that neurons that have elevated dnKCNQ2 (but not CREB) levels are also preferentially recruited into the memory trace because dnKCNQ2 also acts to increase neuronal excitability. Therefore, Yiu’s research added depth and nuance to Han’s findings, furthering our understanding of the mechanisms by which certain neurons become important for memory formation and expression.

Yiu’s paper was also generally more thorough than Han’s. For instance, Yiu tested overall anxiety measures in mice using the Open Field Test (OFT) and Elevated Plus Maze Test (EPT) to make sure increased overall anxiety as a result of elevated neuronal excitability wasn’t the reason for memory enhancement, whereas Han did not carry out such thorough testing to ensure potential behavioral or emotional side effects of elevated CREB levels were not behind the observed effects in memory. 

It would be interesting to see how these studies relate to last week’s papers, particularly Ramirez’s 2013 research on the creation of false memories in the hippocampus through reactivation of memory engram cells. As Yiu showed that elevated neuronal excitability enhances memory formation, is it possible that an increase in neuronal excitability caused by cellular reactivation could factor into the formation of these new false memories? It is important to note, however, that Ramirez’s research was done in the dentate gyrus and not the LA. While it makes sense that the amygdala would be involved in a process as emotionally salient as fear memory formation and expression, it is interesting that Han and Yiu’s research was conducted in this brain region instead of in the hippocampus, which is more commonly associated with memory processes. In line with this, future research could maybe try to replicate these findings in hippocampal structures. Finally, I was left wondering whether the findings of these papers would hold true for other types of memories, perhaps ones that were linked to more positive emotions than fear, or memories not associated with emotional salience at all. 

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