Reconsolidation and Fear Extinction: An Update.

Fear memories can be updated behaviorally by delivering extinction trials during the reconsolidation window, which results in a persistent attenuation of fear memories (Monfils et al., Science 324:951-955, 2009). This safe and non-invasive paradigm, termed retrieval-extinction (or post-retrieval extinction), has also been found to be successful at preventing the return of fear in healthy fear conditioned humans (Schiller et al., Nature 463:49-53, 2010), and in the time since its discovery, there has been an explosion of research on the use of retrieval-extinction in fear memories in humans and other animals, some of which have found a long-term reduction in conditioned responding, and some who have not. These discrepant findings have raised concerns as to whether retrieval-extinction really results in updating of the original fear memory, or if it simply enhances extinction. We will first review the progress made on elucidating the cellular mechanisms underlying the fear attenuating effects of retrieval-extinction and how they differ from traditional extinction. Special attention will be paid to the molecular events necessary for retrieval-extinction to successfully occur and how these reconsolidated memories are represented in the brain. Next, we will examine the parameters that determine whether or not a memory will be updated via extinction during the reconsolidation window (also known as boundary conditions). These boundary conditions will also be discussed as possible explanations for discrepant findings of the retrieval-extinction effect. Then we will examine the factors that can determine whether an individual's fears will successfully be attenuated by retrieval-extinction. These individual differences include genetics, age, and psychopathology. Finally, we will discuss recent attempts to bring the retrieval-extinction paradigm from the bench to the bedside for the behavioral treatment of anxiety and trauma disorders.