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Blog 4: Recruiting neurons to a memory trace

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The papers this week discuss how a small population of lateral amygdala (LA) neurons are preferentially activated by fear memory expression, plus what factor(s) contribute to these neurons being recruited to the memory engram. Although both papers were quite interesting, I found myself puzzled by some of the specific experimental design choices. Beyond this, I also felt like there are several qualifiers to the researchers’ conclusions that left me intrigued but skeptical for how these findings can become clinically relevant.

Namely, what exactly is the relevance in the strength difference of an auditory fear memory? Han et al (2009) frequently referred to their findings in the contexts of “a weak memory” versus “a strong memory” or even “an intense protocol” without much further explanation. Even when Yiu et al (2014) talked about the effects of two different excitatory (dnKCNQ2) and inhibitory (Kir2.1) K+ channels, they specifically mention the use of weak auditory fear conditioning. My best response is that there simply exists some threshold for the intensity of the foot shock in order to elicit a baseline fear/freezing response that was determined and validated in previous studies. However, Han et al (2009) drew one conclusion that the reversal of CREB-enhanced memory was not due to memory extinction because their control groups froze robustly - yet they did not include any measure of baseline freezing. They also only used male mice, which is in (amazing) contrast to Yiu et al (2014) who used both male and female mice and reported that they saw no difference in baseline (pre-tone) freezing.

Another, but related, question I noted was in regard to general behavioral measures of fear other than freezing (or darting in females). Yiu et al (2014) did a control experiment looking for baseline levels of anxiety-like behavior through the elevated plus maze and open field test, and although I do agree this is absolutely relevant to fear measures, I cannot help but feel like the strokes being made are too broad from one thing to the next. Specifically, I’m not convinced that Yiu et al (2014) observing increased freezing in hM3Dq + CMO animals is enough to say that it "enhances memory formation." What it is actually telling, I am not quite sure. I feel as though there needs to be more confirming evidence outside of just freezing levels in this select population of neurons to indicate that a memory was truly formed.

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