Special issue on consolidation, reconsolidation and extinction

Abstract

The notion that our memories are not fixed but evolve and change over time can be traced back to Ribot (1881). He noted in his classic monograph (Les Maladies de la Memoire) how amnesic patients often had little memory of their recent past but could remember many things from way back in their lives. Ribot suggested that a biological process unfolds over time which makes memories progressively stronger so that traumatic brain injury disrupts recollection of the recent but not distant past. Subsequently, Muller and Pilzecker (1900) put forward a cognitive ‘retroactive interference’ account of the same phenomenon whereby shortly after new information is encoded, it could be disrupted by learning other similar information. It is now accepted that memories undergo multiple processes of consolidation. Immediately after learning, memories are labile and can be disrupted by interference, amnestic drugs or trauma. In the hours after learning, they are ‘consolidated’ at the neuronal level and over time become increasingly stabile and cortically distributed through a process of ‘systems consolidation’. Memory consolidation involves a brief cascade of molecular, cellular and epigenetic events that alter synaptic efficiency followed by more prolonged systems-level interaction between the hippocampus (which stores new memories) and areas of the cerebral cortex (supporting older memories; e.g. McGaugh 2000). There is now considerable evidence that for a short while after learning—during the consolidation interval—memories are vulnerable to disruption not only by new learning of other material but also by protein synthesis inhibitors like anisomycin, electroconvulsive shock, beta-blockers andN-methyl D-aspartate (NMDA) antagonists. Disruption does not occur outside this consolidation interval, suggesting that these memories are in a fixed, consolidated, stable state and remain so potentially indefinitely (McGaugh 1966; Squire and Alvarez 1995). Over the past decade, there has been an accumulation of evidence that previously consolidated memories can, in certain circumstances, also be disrupted or even enhanced (c.f. Nader et al. 2000; Dudai 2006; Hardt et al. 2010; Milton and Everitt 2012). In such conditions, those established memories can be made labile again through the reactivation of the memory trace. This reactivation—brought about by associated environmental cues or re-presentation of learned material—and associated memory retrieval can initiate a period of instability during which the memory itself can be strengthened or updated or disrupted prior to being reconsolidated. Similarly, reconsolidation can be chemically disrupted, resulting in potential memory erasure. Just as protein synthesis is required for consolidation of memories, it is also essential for the reconsolidation of memories after reactivation. As Nader et al.'s (2000) landmark study showed, blocking protein synthesis by infusing anisomycin into the basolateral amygdala of rats after reactivating a cued fear memory drastically reduced fear behaviour (freezing) to the cue the next day and for 14 days after. Retrieval can thus return memories to a plastic, malleable state. What role reconsolidation plays in real life is still debated (Dudai 2006). From an evolutionary perspective, reconsolidation could serve an important adaptive role of updating prior knowledge at the time of retrieval to maintain the predictive validity of memories. For example, updating of memory to incorporate changes in environmental dangers can be critical to an animal's survival. Indeed, prediction error-based mismatch between expected and actual outcomes appears to be a necessary condition for memory reconsolidation (Osan et al. 2011; Sevenster et al. 2013). As human cognitive function uses memory to interpret and act upon current events and envisage future events, memory updating is an essential means of keeping memory relevant. The other side of this coin is that, by H. V. Curran (*) Clinical Psychopharmacology Unit, University College London, Gower Street, London WC1E 6BT, UK e-mail: v.curran@ucl.ac.uk