The role of the mTOR pathway in fear learning

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This research program investigates the molecular mechanisms underlying associative and non-associative fear memory. We have recently shown that the mammalian target of rapamycin (mTOR) pathway is critical to associative fear memory (Blundell et al., 2008). Using the classical fear conditioning paradigm in which an animal learns to associate a context with an aversive stimulus (in this case, a shock), we showed that a systemic injection of rapamycin, an inhibitor of the mTOR pathway, during consolidation (following fear training) or reconsolidation (following a reminder of the fearful event) blocked subsequent memory for the aversive event. While these data suggest that the mTOR pathway mediates associative fear memory, it is unknown if it also mediates stress-induced long lasting fear sensitization (e.g. following exposure to a predator), a non-associative fear memory. Thus, the primary goal of my proposed program of research is to determine if the mTOR pathway is not only critically involved in associative fear memory, but also stress-induced non-associative fear memory. This will be a first step in determining whether the molecular mechanisms underlying associative fear memory are similar to those underlying non-associative fear memories. A better understanding of the factors contributing to fear memories will provide valuable insight into the nature of pathological fear disorders such as posttraumatic stress disorder and phobias. Ultimately this knowledge will aid in the development of novel drugs to treat these disorders.