CREB and Fear Memory Learning - Annissa DeSilva



Han et al. and Yiu et al., investigated the neuronal components that allocate neurons in the lateral amygdala (LA) and how they become associated in a particular memory trace. Both found that neurons over expressing CREB were recruited into the memory trace and enhanced fear memory learning. Yiu specifically finding that CREB activity related to increasing the neurons excitability before the fear learning “primed” the neuron to encode for the memory trace associated with that event. This finding is very interesting and elaborates on the process of fear acquisition however both studies used CREB vectors to allow neurons to over express CREB. When reading both studies, the use of CREB vectors really stood out to me and made me wonder if CREB expression in neurons in the LA truly differentiated, and if so to the extent of the “over-expression” that was emulated in the study. Meaning, both researchers artificially created over expressing CREB neurons, but does this CREB expression pattern naturally exist within LA neurons? Perhaps it warrants more research, but I would be interested in seeing how endogenous CREB expression in LA neurons varies and potentially what influences some neurons to have increased CREB expression compared to others at particular moments in time.
Han also found that selectively deleting neurons over-expressing CREB reversed fear enhancement and ablating CREB expressing neurons after fear memory testing blocked the expression of the fear memory. Han concludes that this blocked fear expression implicates the neurons in the neuronal trace in long term fear memory expression. I found this to be one of the most interesting findings of the paper, specifically due to its relation to the clinical treatment of Post-traumatic stress disorder (PTSD). Given that this clinical cohort displays an exaggerated fear response related to stimuli, erasing neurons in the memory trace associated with a traumatic event, or reducing the emotional salience associated with the event seems like a valid treatment option. I think this is very relevant especially considering that some studies have found that those with PTSD have decreased ability for fear extinction (Milad. et al., 2009) which impacts PTSD recovery. Due to inability to elevated fear response by association (fear extinction) the idea to erase or inhibit neurons in the fear memory trace associated with the event may be able to alleviate this heightened response in a different manner.

Citations:
Milad, M. R., Pitman, R. K., Ellis, C. B., Gold, A. L., Shin, L. M., & Lasko, N. B. (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. PsycEXTRA Dataset. doi:10.1037/e717692011-019

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