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Fear Memory Traces, Han & Yiu

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Similar to the Ramirez papers studying memory engrams, the papers by Han et al and Yiu et al studied memory traces related to fear. However, Han and Yiu specifically studied fear memories in the amygdala rather than the hippocampus. Specifically, Han and Yiu studied the lateral amygdala (LA) and the transcription factor CREB in auditory fear conditioning. Han’s paper, published in 2009, answered the question, “is CREB necessary in creating a fear memory trace?” Yiu’s paper, published in 2014, built off of Han’s paper to answer the questions, “are certain neurons in the LA responsible for creating a fear memory trace? If so, by what mechanism?”

The Han paper, in my opinion, was pretty straightforward and gave good insight about CREB and its function in the LA. To put it simply, Han et al reported that, without CREB, the LA cannot form a fear memory. The techniques used were clean, and the results of inactivating neurons overexpressing CREB showed robust effects on freezing. Though Yiu et al were working on a related topic, their techniques relied heavily on transgene expression through viral vectors. Although Yiu et al saw robust effects with their methods, the complex experimental techniques always make me skeptical until another project is able to reproduce their effects. Additionally, the use of specific transcription factors like CREB and specific ion channels (both naturally occurring and transgenic, i.e., KCNQ2, KCNQ3, and dnKCNQ2) may show effects in mice as model organisms, but may not translate to human physiology. For these reasons, I am not completely convinced by the results reported by the Yiu paper.

The Han and Yiu papers both thoroughly studied the LA with respect to the formation and retention of a fear memory trace. Although they showed specific molecular mechanisms underlying these fear memories, their focused attention on the LA makes me wonder what the roles of the other subdivisions of the amygdala are. The Yiu paper includes the central and basal amygdala (CeA and BA, respectively) in their experiments, but show that they are not involved in enhancing a fear memory like the LA. Does this imply that the CeA and BA are involved in emotions other than fear? The amygdala is typically implicated in fear-related behaviors, but is it possible that the CeA and BA discretely contribute to behaviors related to other emotions such as happiness and sadness? I think these would be interesting topics to explore more.

One (very random) thing that I noticed about the Yiu paper was how quickly it was accepted for publication after being submitted—22 days! Does this mean that this is accepted as a new standard of truth for the formation of fear memories in rodents? Maybe the publication process does not depend on the dates listed on the paper, but if the paper truly was published 22 days after submission, I’m very impressed.

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