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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