Reconsolidation and the Dynamic Nature of Memory

Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation takes place only once per LTM item. Research on reconsolidation was revitalized only more than a decade ago with the demonstration of reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat) subserved by an identified brain circuit (basolateral amygdala). Since then, reconsolidation has been shown in many studies over a range of species, tasks, and amnesic agents, and cellular and molecular correlates of reconsolidation have also been identified. In this review, I will first define the evidence on which reconsolidation is based, and proceed to discuss some of the conceptual issues facing the field in determining when reconsolidation does and does not occur. Last, I will refer to the potential clinical implications of reconsolidation.Learning and memory are commonly depicted as going through a set of phases. There is the learning or encoding phase, in which information is acquired, by stabilization phase, in which specific mechanisms are engaged to stabilize initially unstable new information (referred to as synaptic consolidation) (Glickman 1961; McGaugh 1966), the “storage” or maintenance phase, during which other mechanisms are involved to maintain the memory, and the retrieval phase, in which specific mechanisms permit a memory to be retrieved (Miller and Springer 1973; Spear 1973). For a long time, from a neurobiological perspective, only acquisition and memory stabilization (Martin et al. 2000; Kandel 2001; Dudai 2004) were considered to be active phases, in the sense that neurons had to perform certain computations or synthesize new RNA and proteins for these phases of memory processing to be performed successfully. After acquisition and stabilization, all other phases were implicitly thought by many to be passive readout of changes in the circuits mediating the long-term memory (LTM). However, the picture has now changed and the maintenance of memory is portrayed as an active process. One of the reasons for this change is the demonstration that a consolidated LTM can become susceptible to disruption and restoration, a process termed “reconsolidation” (Spear 1973; Nader et al. 2000; Sara 2000). There are now detailed molecular and cellular models of this time-dependent active memory phase.This review will first describe the logic of the findings that brought the existence of the consolidation process to light. I will then describe how we concluded that a consolidated memory undergoes reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat). I will then refer to the range of species, tasks, and treatments in which reconsolidation have been reported. One aspect of reconsolidation that has attracted experimental attention involves the finding that there seem to be conditions that facilitate, inhibit, or even prevent reconsolidation from occurring. I present an approach that could help to identify such conditions. Last, I will discuss potential clinical implications of reconsolidation.