PI3K-Akt signaling in the basolateral amygdala facilitates traumatic stress enhancements in fear memory.

Background A core symptom of post traumatic stress disorder (PTSD) is persistent fear memory, which can be defined as fear memory that is resistant to updating, inhibition, or extinction. PTSD emerges after traumatic stress exposure, but neurobiological mechanisms via which traumatic stress leads to persistent fear memory are not well defined. Akt signaling within the amygdala (Amy) is enhanced with traumatic stress and phosphatidylinositol kinase 3 (PI3K) activation of Akt within the basolateral amygdala (BLA) has been implicated as critical to fear memory formation. These findings raise the possibility that traumatic stress enhances PI3K → Akt signaling in the BLA, which leads to persistent fear memory. Methods To test this hypothesis rats were exposed to traumatic stress, using the single prolonged stress model, and changes in Akt phosphorylation (pAkt) were assayed in the Amy at 0 and 30 min after fear conditioning (FC). In a separate experiment we inhibited PI3K → Akt signaling in the BLA prior to FC and observed the effect this had on acquisition, expression, and extinction of FC in stressed and control rats. Results Enhanced pAkt in the Amy at both time points was observed in stressed rats, but not in control rats. PI3K → Akt inhibition in the BLA had no effect on freezing in control rats, but decreased freezing during extinction training and testing in stressed rats. Conclusion These findings suggest that PI3K → Akt signaling in the BLA could be a mechanism via which traumatic stress leads to fear memory that is resistant to extinction.