Encoding of Fear Memory in High and Low Fear Mice

Post traumatic Stress Disorder (PTSD) is a debilitating and often chronic condition resulting from exposure to life threatening trauma and stress. It affects both military persons and civilians.  Understanding how the brain is involved in PTSD is critical to more effective treatment.  A prominent animal model used to study different aspects of PTSD is rodent fear conditioning.  Fear conditioning is a behavioral method by which an organism, oftentimes a rodent, learns to fear new stimuli.  In the fear conditioning method, an emotionally neutral stimulus such as a light or a tone (conditioned stimulus; CS) is presented to the rodent at the same time as a small electric shock (unconditioned stimulus; US).  Upon one or several presentations of the CS and US together, the animal learns to fear the CS alone.  In this way, fear is developed in the rodent.

One brain region that is working during fear conditioning is the amygdala.  The activation of various proteins in the amygdala are necessary for the development of a fearful memory.  In particular, phosphorylated mitogen-activated protein kinase (pMAPK) has been shown to be particularly important in the formation of a fear memory in the amygdala.  We are beginning to understand how pMAPK is organized in the amygdala during the formation of fearful memory.  What we do not know is how memory strength is reflected in structural organization of pMAPK expression. Individual genetic predisposition likely influences the circumstances under which a strong or weak memory in formed. Understanding how pMAPK is organized in weakly or strongly encoded fear memory is crucial to understanding how fearful memories are acquired and stored in the amygdala.

In this study we aim to provide fundamental data about the organization of pMAPK in the amygdala in weakly or strongly encoded memories.  Using mice selectively bred for high or low freezing behavior following fear conditioning, we plan to test how genetic and potentially epigenetic predisposition influences memory strength. Following fear conditioning, we will use brains taken from anesthetized/euthanized mice to study pMAPK organization and tissue content of pMAPK in the amygdala. 

Relevance: PTSD is a significant psychobiological pathology within the military population.  A key challenge for military nursing is to recognize susceptibility to fear-related illness such as PTSD in ourselves and others.  This research seeks fundamental knowledge into how lasting emotional memories are stored in the brains of high and low fear animals. Identifying differences in the microcircuitry involved in the encoding of traumatic memory may lead to more individualized care and improved clinical interventions.

Final Report is available on NTRL: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2014101...