View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Current Biology Vol 23 No 17 R746 emerged from the pattern of amnesia consequence of this dynamic process Memory collectively caused by all these is that established memories, which reconsolidation different types of interventions. have reached a level of stability, can be Memory consolidation appeared to bidirectionally modulated and modified: be a complex and quite prolonged they can be weakened, disrupted Cristina M. Alberini1 process, during which different types or enhanced, and be associated and Joseph E. LeDoux1,2 of amnestic manipulation were shown to parallel memory traces. These to disrupt different mechanisms in the possibilities for trace strengthening The formation, storage and use of series of changes occurring throughout or weakening, and also for qualitative memories is critical for normal adaptive the consolidation process. The initial modifications via retrieval and functioning, including the execution phase of consolidation is known to reconsolidation, have important of goal-directed behavior, thinking, require a number of regulated steps behavioral and clinical implications. problem solving and decision-making, of post-translational, translational and They offer opportunities for finding and is at the center of a variety of gene expression mechanisms, and strategies that could change learning cognitive, addictive, mood, anxiety, blockade of any of these can impede and memory to make it more efficient and developmental disorders. Memory the entire consolidation process. and adaptive, to prevent or rescue also significantly contributes to the A century of studies on memory memory impairments, and to help shaping of human personality and consolidation proposed that, despite treat diseases linked to abnormally character, and to social interactions. the fact that it is a long process that consolidated memories. As we will Hence, understanding how memories progresses through a sequence of see below, however, reconsolidation are formed, stored, retrieved, modified, changes, memory formation involves a processes in different systems/ updated and used potentially impacts single type of stabilization process, and networks have distinctive features, many areas in human life, including once a memory reaches a consolidated suggesting that potential treatments mental health. level it becomes insensitive to will need to be flexibly tailored to The traditional view of memory disruption. specific circumstances. storage assumes that each time we More recently, this classic view Reconsolidation has a variety of remember some past experience, the of the consolidation process has important theoretical and practical original memory trace is retrieved. undergone revision. Drawing upon implications, and has stirred a great This view has been challenged by earlier observations, a large number deal of debate. Many questions have data showing that when memories of studies over the last 15 or so been raised in numerous discussions. are retrieved they are susceptible to years have shown that consolidated Why does memory reconsolidate? How change, such that future retrievals memories, which should be insensitive general is this process? Is it simply a call upon the changed information. to amnesic agents, again revert to a duplication of consolidation or does This is called reconsolidation. That vulnerable state if they are retrieved it involve unique mechanisms? Is reconsolidation exists is not at issue, (the trace is reactivated). These active reconsolidation a true, independent but what really reconsolidation is, how (or reactivated) memories can then process, or is it a deceptive effect it occurs, and what it means are heavily again undergo another consolidation that actually involves the regulation of investigated and debated topics. process, which is in many ways similar other memory processes, like retrieval, to that of a new memory (Figure 1). This extinction, and new learning? Can The classical view and the change additional process has hence been reconsolidation offer an opportunity For about a century, the process named memory reconsolidation. to weaken, even perhaps eliminate by which a persistent or long-term Reconsolidation has been found pathogenic memories? We will discuss memory is formed, stored and retrieved for a variety of different kinds of some of these issues here. was believed to be a singular, linear memories (explicit and implicit; process. In brief, it was thought that a aversive and appetitive) in many kinds Why does memory reconsolidate? freshly acquired memory trace remains of organisms (from invertebrates to What is the advantage of having in a fragile state for a limited time humans). It is clear from the results of established memories become labile during which it is sensitive to disruption the large number of studies that have and then restored? The general by a variety of means. Over this time, experimentally addressed the topic that advantage of reconsolidation is that the memory undergoes a series of consolidation is not a singular process it provides the ability to respond in changes in the brain that convert the of stabilization that occurs once for a flexible and adaptive manner to labile entity into one that is stable and each memory. Memories, in other continuously changing environments. long lasting. This stabilization process words, can reconsolidate after retrieval, Evidence revealed that reconsolidation by which a newly formed, labile and this may occur many times. allows changes in memory strength, memory is converted into a lasting and The picture that emerges is that and although still a subject of stable long-term memory is known as long-term memories are stabilized and debates, some authors propose that memory consolidation. then de-stabilized and re-stabilized reconsolidation mediates updating of In its early fragile state the memory according to the reactivation schedule memory content. is sensitive to many different types of of their traces. Hence they appear If a learning experience reoccurs, interference, including behavioral or to undergo many reconsolidation memory may become labile, and cognitive interference, brain trauma, cycles in the course of their existence. over time, through mechanisms of seizures, and pharmacological or Memory storage is thus a dynamic reconsolidation, be re-stabilized molecular manipulations. The definition process and a consolidated memory and strengthened. The same occurs and features of memory consolidation is far from being ‘fixed’. One important when instead of a second learning Special Issue R747 event the memory is retrieved by a Retrieval of reminder of the learned experience. experience Retrieving, hence reconsolidating, memories may provide the advantage of strengthening adaptive memories, without requiring re-exposure to Learning Storage Retrieval Retrieval the original learning situation. This is likely to be useful in the case of rewarding as well as aversive, painful and/or dangerous events, especially when the memories are acquired Retrieval of last after a single learning experience storage and cannot benefit from repetition. Clearly different conditions evoking reconsolidation, whether through Learning Storage Retrieval Storage Retrieval repetitions of the learning experience (multiple training trials) or different types of retrieval, may result in distinct storage patterns. With multiple Current Biology training trials the same experience is presented during the initial learning as Figure 1. Two views of memory. well as the reactivating trials; hence The conventional view was that memories are stored once and each time the memory is ac- the activation and recruitment of tivated (remembered) a trace of the original experience is retrieved (top). According to the re- similar networks are likely to occur. consolidation view, memories are susceptible to change each time they are retrieved. The next In contrast, reconsolidations evoked time the memory is activated the version stored during the last retrieval, rather than the version stored after the original experience, is called up. by other types of experience, such as retrieval events that are different from the original learning experience, are amnestic treatments, using these paired, motor memories, and in likely to activate and recruit different interferences does not distinguish hippocampal, amygdala and cortical- networks. The reverse is also true: whether there are parallel traces dependent memories. Although there through reconsolidation, memory of consolidation as opposed to are few examples of disagreement, in can also be weakened. For example, stabilization of an updated version of the majority of cases the disruption a threat stimulus that leads to the original trace via reconsolidation. of memory reconsolidation produces heightened physiological arousal can Methods of selective dissociation a persistent decrease in memory result in a stronger memory but one between new consolidation and retention, as shown by molecular and that leads to less arousal can weaken reconsolidation will be needed to cellular readouts in animals, and also the memory. address this issue. A model that recently confirmed by imaging studies In addition to memory strengthening explains why the similarity between in humans. and weakening, retrievals can modify the events present at memory retrieval Many different types of reactivation the trace content. Hence one function and