The Contribution of the Prefrontal Cortex in Fear Memory Specificity

Several mental disorders present with symptoms related to inaccurate fear memory discrimination, including post-traumatic stress disorder (PTSD), in which a non-aversive stimulus resembling a previously experienced aversive situation triggers a fear response. The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and non-aversive stimuli are unclear. While much research has involved the hippocampus in these processes, more recent studies implicate the medial prefrontal cortex (mPFC). By using a combination of novel behavioral paradigms and viral-mediated genetic manipulation, we were able to disrupt specific processes within the mPFC and measure their effect on fear memory accuracy. We found that several elements important to the cellular mechanisms underlying memory consolidation within the mPFC are required for appropriate discrimination of aversive and non-aversive stimuli with overlapping qualities of similarity. These include cyclic AMP response element binding protein (CREB), CREB-binding protein (CBP) histone acetyltransferase (HAT) activity, and N-methyl-D-aspartate receptors (NMDARs). This work contributes to the growing body of literature on prefrontal contributions to memory systems at the basic level, and can be applied to our understanding of deficient memory specificity found in disorders like PTSD