Trends in Neurosciences
Memory traces unbound
Section snippets
Early studies on reconsolidation
In 1968, the view that memories are consolidated over time into a permanent state was challenged by Lewis and colleagues [16]. In agreement with previous studies, when ECS was given 24 h after fear conditioning it was ineffective in generating amnesia. However, if the memory was reactivated before ECS administration, amnesia was observed the following day. Given that amnesia was not produced in the absence of memory reactivation, the memory is defined as being consolidated by that time.
Erasing fear
Capitalizing on the current knowledge of the locus and mechanisms of fear memory formation, striking support for Lewis’ original finding has recently been reported [19]. An auditory fear-conditioning paradigm, which is now well described 29, 30, 31, was used in conjunction with targeted inhibition of protein synthesis in the lateral nucleus of the amygdala (LA; a nucleus in which protein synthesis is required for consolidation of auditory fear conditioning [32]). Intra-LA infusions of the
Reconsolidation across species
In addition to rodents, cellular reconsolidation with targeted infusions has been reported in both the chick [34] and the crab Chasmagnathus [35]. These findings are further confirmation that reconsolidation is a basic evolutionarily conserved process. In the crab, a contextual fear-conditioning paradigm was used. Re-exposure to the training context the day after training returned the memory to a state that was sensitive to both cyclohexamide and NMDA-receptor antagonist (MK-801) treatments.
Comparison of reconsolidation and consolidation
The findings in chick using one-trial passive avoidance (PA) are the most extensive comparison of consolidation and reconsolidation in a single study. Infusions of anisomycin, or the inhibitor of post-translational glycoprotein fucosylation, 2-deoxygalactose (2-d-gal), into the intermediate medial hyperstriatum ventrale blocked consolidation and reconsolidation [34]. The differences reported were as follows:
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on re-testing, the amnesia produced by blockade of reconsolidation (but not
Transcription versus translation
One of the cardinal rules of consolidation of new memories is that it requires transcription 11, 13. One question concerning reconsolidation has been whether it too would require transcription or whether translation of proteins from dendritic RNAs would be sufficient [42]. This issue was recently addressed using an inducible dominant–negative transgenic mouse in which the function of the transcription factor CREB was compromised in excitatory neurons of the forebrain [49]. Consistent with the
Reconsolidation and extinction
In the typical reconsolidation experiment, the conditioned stimulus is presented without the reinforcer and the memory trace is challenged. Operationally, this is an extinction trial. Extinction is new learning during which an animal begins to learn that the unconditioned stimulus (US) no longer follows the CS. Reconsolidation, however, is posited to be the re-storage of the underlying memory [16]. Thus, at a conceptual level they are distinct but they might involve similar molecular
Systems reconsolidation
In the hippocampus, consolidation occurs at a second level of analysis that is posited to last in the order of weeks for rodents and years in humans, called ‘systems consolidation’ [8]. First described by Scoville and Milner [58], the hypothesis states that the hippocampus plays a time-limited role in memory processing, such that recent memories are hippocampus dependent, whereas older memories are not 59, 60, 61. For the sake of clarity, memories that have become independent of the hippocampus
The qualitative nature of reconsolidation and consolidation
Currently, the issue of whether amnesia is a deficit of storage or retrieval has still not been resolved 9, 65. Thus, although we cannot determine with certainty the qualitative nature of reconsolidation and consolidation, we are in a position to ask whether they are qualitatively similar. If they represent qualitatively similar processes, then they should behave in a qualitatively similar manner in response to different neurobiological challenges across paradigms. However, if they are
New learning versus re-storage
One issue that has been at the forefront of discussions on reconsolidation is the role of new learning. For example, perhaps anisomycin prevents the consolidation of new learning occurring during the reactivation session. In turn, it is the blockade of this new learning, as opposed to the re-storage of the original trace, that is responsible for the behavioural deficit. First, we must bear in mind that consolidation theory explicitly predicts that only new information acquired during a session,
A note from the past
It has been widely questioned whether reconsolidation occurs in humans, following a study demonstrating that ECS impairs new but not old reactivated memories in humans [28]. However, it should be noted that there are several positive findings of reconsolidation in humans 76, 77. The hypothesis proposed and experimental design used by Rubin were based completely on the findings of Lewis’ original reconsolidation experiment. Rubin reasoned that if individuals were forced to focus on the subject
What we have learned and where we are going
Data from a diverse array of species, a variety of paradigms and different molecular technologies have demonstrated that reconsolidation occurs in multiple brain systems and is qualitatively strikingly similar to consolidation. Already implicated in the reconsolidation process are the usual suspects such as NMDA receptors, CREB, new protein synthesis, Fos and zif286. It is clear that reconsolidation has not been universally found and that it is still too early to understand which critical
Acknowledgements
I thank L. de Hoz and P. Frankland for their helpful comments on drafts of this manuscript. This work was supported by grants from NSERC, Human Frontiers of Science Programme and the Volkswagen Foundation. I also thank T. Schallert for bringing the studies in 75, 76 to my attention.
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