Post 4- Excitability and CREB in the competitive encoding of fear memory

The papers this week begin with Han et al., 2009 that described experiments showing the selective erasure of fear memory, with the overarching results depicting how specific neuronal populations exist that selectively code for fear memory within a memory trace. They tested this by pinpointing which neurons under specific conditions were active upon fear memory recall and ablated them to show the disappearance of fear memory recall. The experiments were carried out well with quite robust results, however the most significant part of the paper was their ability to identify the subpopulation of neurons that encoded the fear memory in response to training. It was the discovery of neurons expressing increased levels of CREB that were more likely to encode enhanced fear memory that lead Yiu et al. 2014 to work on finding out the mechanism that allowed for these CREB expressing neurons to selectively encode fear memories. 

Their findings were centered not in the attribution of these neurons in the Lateral Amygdala to CREB expression, but to the high excitability levels of these neurons before and during fear training that allowed them to competitively code and retrieve the fear memory. This hypothesis and experimentation was intriguing as this idea of more excitable neurons “winning” falls in parallel with the Hebbian ideas of “Neurons that fire together wire together.” Results gathered by Yiu et al. 2014, greatly aid in the possible understanding of this mechanism. It is comparable to the idea of synaptic pruning as well, where the increased excitability of neurons are more likely to persist their connections as compared to neurons that are not activated as often.

Han et al. 2009, were able to test this out initially by manipulating CREB levels in Lateral Amygdala neurons and attempting to observe behavior and memory encoding upon overexpression.  This in particular was the key that Yiu et al. 2014 needed to come across their hypothesis that excitability of neurons was what made them more likely to be part of the memory trace. Yiu et al. 2014, used this method as well as expression of a dominant negative KCNQ2 mutant, synthetic receptor activation and finally optogenetics to show that the ability of this specific population of neurons to competitively encode memory was not due to expression of CREB alone, but due to the increased excitability of the neuron, before or during training, that gave it a higher chance of being part of the memory trace. 

The succession of research following Han et al. 2009 is what excites me most about science, as it is the constant building of knowledge and improving upon previous work that allows scientists to follow new paths and lead to novel discoveries. Yiu et al. 2014, uncovered a mechanism that using previous research that will have undoubtedly inspired research after their own.