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Post 4: CREB and fear memory extinction/enhancement

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Upon reading and rereading Han et al. (2009), I found myself left with many questions. I wondered why LA neurons with increased CREB are preferentially activated by fear memories/recruited for memory traces, whether CREB has the same effect in other brain regions, and whether its effects are limited to auditory fear memories, to name a few. Upon reading Yiu et al. (2014), many of my uncertainties stemming from Han et al. were clarified, but again I was left with questions regarding methods and implications of this study for future research. 

While Yui was very comprehensive in its methods of investigation, experimental groups, and controls, I wondered why there was not a greater reliance on temporally precise methods of neuronal activation/excitement such as hM3Dq DREADD and especially optogenetics. It seems that the relatively large window of the transgene expression using HSV could lead to enhanced encoding of memories outside of the fear training and/or testing, and an expansion of their more precise methods could have generated even more accurate results. Additionally, there seemed to be a focus on the activation of small portionsof LA neurons for increased fear memories, but there was no investigation or mention of what happens when larger proportions of LA neurons are activated. Because it was found that the same small number of neurons was involved in memory traces in these investigations, I would hypothesize that a larger number of activated LA neurons would lead to a memory trace of the same size that is potentially weaker due to increased competition between cells overexpressing CREB. 

On a broader level, I considered the implications of this research and how its findings may be applied in future research or therapeutic methods. One of my most pressing questions while reading both of these papers was whether CREB overexpression enhances memory traces in other brain regions and/or for types of memories other than auditory fear memories that may be more complex. While Yui did confirm that there is no memory enhancement with CREB overexpression in the lateral or central amygdala, I wonder if this is due to the fact that only auditory fear memories were investigated, and I would be interested in an investigation of whether CREB activity in brain regions outside the amygdala are involved in non-fear memory traces. As for the types of memories influenced by CREB overexpression, it is essential for potential clinical applications of these findings to know whether CREB overexpression may be involved in the enhancement of more complex fear memories, as seen in PTSD. If so, these LA neurons could be a future target for treatment of PTSD in humans, offering a way to extinguish specific fear memories without damaging more than a small number of neurons. 

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