While preparing my presentation for these papers, I
constantly noted that I didn’t have a large problem with the way that either
experiment was performed. Especially the Han paper, which was short and sweet,
but still consisted of a structure designed to check off logical boxes step by
step. The experiment was clever, and my main qualm with the paper is that it
did not address the directionality of neurons expressing high levels of CREB –
should the reader be inclined to think of these neurons as important in terms
of input from the hippocampus or output to different areas? Although it was not
explicit, the closest the authors came, in my opinion, was when they discussed
a potential design flaw in their experiment being the neglect of memory
reconsolidation after performing a Test #1 (before injection of DT and
subsequent ablation of CREB-cre neurons). To me, reconsolidation seems like it
should have more to do with hippocampal inputs to the LA rather than any
output, but the possibility of this confounding variable was short-lived and
thus no directionality was discussed.
The Yiu paper, which was a perfect logical progression from
the Han paper, was also extremely clever. Obviously, it is more difficult to
test sufficiency (as the authors do in this paper by activating cells) than
necessity (as Han does by getting rid of certain neurons). But, I did feel that
the decision to use optogenetic techniques as a verification at the end of the
paper leads the results to be lacking in subtlety: optogenetic techniques fail
to qualify what mechanism a cell uses to activate something. Instead of this
broad-stroke measure, the authors could have done a longer and most definitely
more expensive experiment to attempt to rule out exactly how these cells become
excited to produce the response studied. Overall, though, the Yiu paper also
appears to be nearly airtight to me.
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