ApoE Isoform-Dependent Effects on Extinction of Contextual Fear Memory and Passive Avoidance Memory

Following exposure to trauma, avoidance behavior can be protective but also contribute to severe symptoms and interfere with exposure-based therapy. Extinction of fear conditioning by exposure to the same environment or environmental cues that were present during the initial traumatic event but without including the aversive stimulus or stimuli is often used to study post-traumatic stress disorder (PTSD), a condition characterized by an inability to suppress conditioned fear responses. A limitation of this paradigm is that one cannot avoid the context or cues associated with the initial traumatic event. In contrast, in the passive avoidance test, one can escape the environment associated with the aversive stimulus. Genetic factors might modulate the ability to extinguish fear memory. In this study, we compared the effects of distinct human apoE isoforms on the extinction of contextual fear and passive avoidance memory, as well as on subsequent activity levels, depressive-like behavior, and hippocampal levels of tau, in targeted replacement mice.