A characteristic symptom of posttraumatic stress disorder (PTSD) is recurrent, intrusive memories of a traumatic experience. The long-term goal of the current project is to use animal models to find clinical tools to treat people with unwanted traumatic memories. This project explores in the rat the idea that disrupting fear memory formation in the aftermath of a traumatic experience may be a useful approach for mitigating PTSD symptoms. This approach derives from consolidation theory, which holds that newly acquired memories are initially labile and stabilize over time into enduring traces. Recent findings from our laboratory show that extinction training given 10 min after fear conditioning (short-interval extinction) disrupts fear memory in a manner that is resistant to recovery by reinstatement, renewal, and spontaneous recovery - three animal model correlates of clinical relapse. Conversely, all three forms of relapse are evident following fear memory disruption by extinction training given 72 hrs after fear conditioning (long-interval extinction). Based on these and supporting biochemical findings it is hypothesized that, unlike long-interval extinction, short-interval extinction disrupts fear memory consolidation via an erasure or """"""""unlearning"""""""" mechanism. Thus, short-interval extinction may serve as a clinically promising tool to disrupt traumatic memories. Yet, it is not always practical to intervene in the immediate aftermath of a trauma, and this approach does not help extant PTSD patients. However, a phenomenon called reconsolidation blockade, whereby stable fear memories may be disrupted if perturbed immediately after reactivation, may prove useful for eliminating long-term fear memories.
The specific aims are to: 1. Provide behavioral and biochemical support for the idea that short-interval extinction disrupts memory consolidation via an erasure mechanism. Using western blot analysis, amygdala neurons will be examined for specific biochemical changes at various time points after fear training and after short-interval extinction. It is predicted that short-interval extinction will reverse certain learning-related biochemical changes observed after training. 2. Combine reconsolidation blockade with short-interval extinction into a new behavioral protocol whereby the reactivation of a mature fear memory is immediately followed by extinction. Using western blot analysis, amygdala neurons will be examined for specific biochemical changes at various time points after memory reactivation and after post-reactivation short-interval extinction. It is predicted that the biochemical changes seen after reactivation will be reversed by immediate post-reactivation short-interval extinction. The long-term goal of this project is to use animal models of fear memory to develop clinical tools to treat unwanted, persistent, and intrusive memories associated with posttraumatic stress disorder (PTSD). PTSD is a debilitating and costly illness of high morbidity, and is major public health concern. Thus, finding tools to mitigate PTSD symptoms is of vital importance to mental health research. ? ? ?
