Public Release:  NYU neuroscientists find long-term memories are surprisingly unstable and impermanent

New York University

Neuroscientists at NYU's Center for Neural Science have discovered evidence that contradicts entrenched psychological and neurobiological models of memory. Karim Nader, Glenn E. Schafe and Joseph E. LeDoux have revealed that the storage and retrieval of long-term memories of fearful experiences are surprisingly unstable. Nader and colleagues found that long-term memories become labile (that is, chemically unstable) every time they are retrieved. In this labile state, long-term memories can be easily altered or disrupted. Furthermore, the researchers found that once a long-term memory is retrieved, it cannot be stored without the synthesis of new proteins.

Nader said, "The traditional model of memory says that new learning is transformed into solid, stable chunks of long-term memory through a one-time process of protein generation known as consolidation. Our findings challenge the model. Consistent with suggestions from the earlier literature we have found that long-term memories enter a chemically unstable state every time they are retrieved. Furthermore, we demonstrated that every time they are retrieved, they must be reconsolidated through the generation of new proteins.

"Although the phenomenon of reconsolidation has been around for a long time, it has not been well-integrated into traditional views of the biology of memory. Our new study closes that gap by showing that reconsolidation occurs within the neural system that actually forms the memory. This could not be done until the memory circuitry was characterized. In our efforts to determine whether and if so how reconsolidation of fear memory works, we therefore built on earlier work in identifying the amygdala as a site of neural changes that underlie fear learning.

"There is a wide range of implications of these findings for both experimental as well as clinical science. On the basic research side, it contributes in a fundamental way to our understanding of how memory processes in the brain function. Specifically, it demonstrates that the mechanisms mediating memory are much more dynamic than initially thought. Indeed, it may have explanatory powers for phenomena like false memory syndrome. For example, imagine you were at a scene of a crime. Someone asks you if you remember a person with a red jacket there (in reality there was noone with a red jacket there). When you call up the memory of the crime scene it becomes labile, creating an opportunity for suggested or created images of a person with a red jacket to become stored with the original memory undergoing reconsolidation. Therefore, the next time you think of a crime scene there may be someone wearing a red jacket at the scene of the crime and, to the subject, it1s completely accurate. On a clinical level, it suggests a way of interfering with memory disorders such as post-traumatic stress disorder where the strength of traumatic memories impairs normal functioning. In this case, if the traumatic memory can be reactivated, bringing it into a labile state, then we can pharmacologically block that memory from reconsolidating. In principle, this should eliminate the memory."

Nader's research was conducted using laboratory rats. It focused on the lateral and basal nuclei of the amygdala (LBA), which are believed to be a site of memory storage in fear learning. By activating a conditioned memory (which has already undergone consolidation) and then infusing anisomycin - a protein-synthesis inhibitor - the researchers were able to eliminate the memory. This effect was produced regardless of whether reactivation/anisomycin infusion was performed 1 or 14 days after the memory was originally conditioned. Furthermore, the same treatment with anisomycin, in the absence of memory reactivation, left memory intact. And consistent with a time-limited role for protein production in consolidation, delay of the anisomycin until 6 hours after reactivation left the memory intact.

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The research will appear as a letter in the August 17th issue of Nature. The title of the article is "Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval." The authors of the letter are Karim Nader, Glenn E. Schafe and Joseph E. LeDoux. Nader is a postdoctoral fellow in the laboratory of NYU neuroscience professor Joseph E. LeDoux.

Karim Nader received his Ph.D. from the University of Toronto under the supervision of Derek van der Kooy. After completing his Ph.D., which was aimed at elucidating how many motivational systems there are in the brain, he moved to NYU to commence post-doctorate work with Joseph E LeDoux. In the last three years, he has published work addressing the neural organization of fear system at a systems, neurochemical, and molecular levels of analysis.

This research was supported by grants from the National Institute of Mental Health, the W.M. Keck Foundation and a Human Frontiers of Science Fellowship.

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