Impact of Prior Stress on Fear Extinction and Hippocampal ERK1/2 Phosphorylation State in a Mouse Model of Post-Traumatic Stress Disorder

As of 2010 there have been 66,935 deployed members of the United States Armed Forces who have been diagnosed with post-traumatic stress disorder (PTSD). One of the main treatments for PTSD is Trauma-Focused Cognitive Behavioral Therapy, which involves exposing individuals to situations or thoughts reminiscent of previous traumatic events and replacing them with non-threatening associations. This treatment is similar to fear extinction, a form of inhibitory learning that allows for the adaptive control of conditioned-fear responses. Previous research has shown that acquisition of fear extinction is dependent on mitogen-activated protein kinase/extracellular-signal regulated kinase (MAPK/ERK) signaling. Herein, we aim to determine i) the association between extinction of trace-conditioned fear and altered ERK signaling in the hippocampus and ii) the impact of previous stress exposure on fear extinction acquisition. We predict to see a direct correlation between acquisition of fear extinction and activation (phosphorylation) of ERK1/2. C57BL/6J male mice were exposed to clean (control) or rat-soiled bedding (predator odor stress), then subsequently trained using a trace fear conditioning protocol. After the mice underwent extinction training, the hippocampus was isolated and the postnuclear fraction was prepared. Recordings of conditioned responses during the extinction procedure will be analyzed using freezing as a read-out and ERK1/2 activation state will be determined in the tissue preparations using Western Blotting. These studies may have applications in identifying mechanisms for drug targeting in the treatment of PTSD, where relapse of fear is an issue.