Memory Reconsolidation

Cristina M. Alberini

• Publisher: Academic Press
• Year: 2013
• Print ISBN: 9780123868923
• eBook ISBN: 9780123868930
• Topic: Psychology
• Subtopic: Cognitive Psychology & Cognition
• Index: Psychology

As little as 10 years ago, it was believed that memory went from short to long term via one consolidation practice that made that memory intractable. Since then, research has shown that long-term memories can be activated, modified, and reconsolidated in their new form. This research indicates that memories are more dynamic than once believed. And understanding how this process works and helping people to redefine established memories can be clinically useful if those memories lead to problems, as is the case in post-traumatic stress disorder.This book provides a comprehensive overview of research on memory reconsolidation; what this has to say about the formation, storage, and changeability of memory; and the potential applications of this research to treating clinical disorders.- Presents both neuroscience and psychological research on memory reconsolidation- Discusses what findings mean for understanding memory formation, storage, and retrieval- Includes treatment applications of these findings

Chapter 1

The Discovery of Memory Reconsolidation

Karim Nader, McGill University, Montreal, Canada

This is an exciting time to be studying learning and memory. Prior to the year 2000, only initial acquisition and memory stabilization, or synaptic consolidation (Dudai, 2004; Kandel, 2001; Martin, Grimwood, & Morris, 2000), were so-called “active” processes, in that they required neurons to implement metabolic and morphological changes that are thought to depend on the synthesis of new RNA and proteins. Once these changes were in place, so it was commonly believed, all other memory processing phases were essentially akin to passive readouts of long-term memory (LTM). Although this was the mainstream opinion, there were some who did not agree with this model, pointing to the possibility that phases of plasticity may be present not just at the birth of a new memory (Lewis, 1979; Miller & Marlin, 1984; Spear & Mueller, 1984).

It is somewhat ironic that this once minority opinion has become the new de facto standard within the past 12 years, as described in more detail later. First, largely through the pioneering work of Todd Sacktor, we now know that memory maintenance appears to be maintenance as an active biological mechanism. There may be a continuous battle being played out between the forces of memory erasure versus maintenance (Migues et al., 2010; Pastalkova et al., 2006; Sacktor, 2010, Shema et al., 2011). This body of work has identified the constitutively active protein kinase M zeta (PKMζ), an atypical isoform of protein kinase C, as critical for sustaining many types of LTM (Sacktor, 2008). It has been shown in many tasks and brain regions that transient inactivation of PKMζ results in the loss of established LTM. Work has shown that the persistent action of PKMζ keeps GluA2-containing AMPA receptors (GluA2 AMPARs) at the postsynaptic density (Migues et al., 2010) and that this continuous regulation of GluA2 AMPAR trafficking maintains LTM (AMPARs are a core part of the biological substrate of memory, mediating the vast majority of excitatory neurotransmission in the brain).

Second, retrieval is now firmly established as the opposite of the once envisioned passive readout of memory, and its mechanisms and consequences are the topic of much exciting research, to which the body of work assembled in this book gives testimony. All this work is based on the peculiar phenomenon that a fully consolidated memory, when recalled, can return to an unstable state from which, in order to persist, it has to be restabilized. This process of restabilization, which was first demonstrated by Lewis and Sherman’s group (Misanin, Miller, & Lewis, 1968; Schneider & Sherman, 1968), is now referred to as reconsolidation. Now, for the second time in the history of our field, there is accumulating evidence that this memory process does indeed exist (Alberini, 2011; Dudai, 2012; Hardt, Wang, & Nader, 2009; Lewis, 1979; Miller & Springer, 1973; Nader & Hardt, 2009; Sara, 2000; Spear, 1973): Retrieval can cause the retrieved memory to reconsolidate, and disrupting this process will impair it.

Consolidation theory is a tale of two gradients describing conceptually related phenomena. On the one hand, there is the concept now referred to as synaptic consolidation. For more than 100 years, it has been known that new memories pass through qualitatively distinct phases over time (Ebbinghaus, 1885; Müller & Pilzecker, 1900; Ribot, 1881): Memories are unstable after acquisition and progressively stabilize over time. Müller and Pilzecker suggested that a perseveration–consolidation process mediates this stabilization. This process is now called “synaptic consolidation,” which is thought to be a ubiquitous property of neurons throughout the brain (Dudai & Morris 2000; Kandel, 2001; Martin et al., 2000). When this process is interrupted before completion, memory will be impaired.

The other time-dependent memory stabilization process was initially described by Theodule-Armand Ribot (1881). Studying patients suffering from amnesia, Ribot reported that patients could not recall recent events but had intact memories from the more remote past (Burnham, 1903; Ribot, 1881). Describing similar cases of retrograde amnesia, Russell and Nathan (1946) commented on the dynamic nature of memory as follows: “It seems likely that memory of events is not a static process” and “the normal activity of the brain must steadily strengthen distant memories so that with the passage of time these become less vulnerable to the effects of brain injury” (p. 299).

Another temporal gradient forms the basis for what is called “systems consolidation.” This notion, proposing that prolonged consolidation reflected memory reorganization over brain systems, began to emerge in studies showing that damage to the medial temporal lobe (MTL) resulted in severe global amnesia, but mostly for recently acquired memories. In a landmark paper, the memory impairments were described for patient HM (the late Henry Molaison), who had most of his MTL removed to relieve intractable epilepsy (Scoville & Milner, 1957). Although Henry Molaison’s intellectual abilities remained intact, the operation left him with a profound impairment in forming new episodic memories (memories of events) and an extensive loss of such memories extending back years before his surgery. He also suffered from anterograde amnesia, the inability to form new memories, which, interestingly, was not global. For instance, he was able to acquire new motor skills, the learning of which he had no conscious recollection. Results from this amnesic patient and others with similar MTL damage suggested that MTL structures, specifically the hippocampus, play a role in episodic, explicit, or declarative memory but not in implicit or nondeclarative memories, such as procedural memories, priming, and conditioned responses. Based on such dissociations provided by many case studies, the presence of a systems consolidation process was proposed in which the hippocampal region served to “prime activity” in cortical areas, where permanent storage took place (Milner, 1966; Squire, Stark, & Clark, 2004). Thus, the hippocampus was thought to be critical during the early, but not later, life of explicit, or episodic, memories.

It is important to note that the neurobiological mechanisms involved in systems consolidation likely engage synaptic consolidation mechanisms (Frankland & Bontempi, 2005). Therefore, reports of reconsolidation at the synaptic level have implications not just for theories of synaptic consolidation but also for theories of systems consolidation.

All consolidation theories posit that once consolidation is complete, a memory will remain in the consolidated state—that is, fixed and stable. In contrast to this expectation, overwhelming evidence suggests that consolidated memories can be transferred again into a labile state, from which they are restabilized by a reconsolidation process. Retrieval appears to be the key process that transfers memory from the stable to the unstable state. This idea is not new to cognitive psychology, in which memory malleability phenomena such as the misinformation effect and hindsight bias have been prominently studied for quite some time. The concept of memory reconsolidation now offers neurobiologically plausible mechanisms that might explain the molecular, cellular, circuit, and brain system processes that underpin these effects (Hardt, Einarsson, & Nader, 2010; Loftus & Yuille, 1984).

1.1 A brief history

Three lines of evidence support the existence of a stabilization period on the order of hours after the acquisition of new memories. First, performance can be impaired if amnesic treatments such as electroconvulsive shock (Duncan, 1949) or protein synthesis inhibitors (Flexner, Flexner, & Stellar, 1965) are given after learning. Second, performance can be impaired if new competing learning occurs after the initial learning (Gordon & Spear, 1973). Third, retention can be enhanced by administration of various compounds after the initial learning, such as strychnine (McGaugh & Krivanek, 1970). Critically, all three manipulations are effective only when given soon after new learning and not when given after a delay. These findings gave rise to theories of synaptic consolidation (Glickman, 1961; Hebb, 1949; McGaugh, 1966).

The initial unstable trace is called “short-term memory,” lasting on the order of hours. With time, the trace enters LTM, at which point it is considered to be consolidated and can no longer be affected by treatments such as those mentioned previously. Thus, if a memory is susceptible to enhancement or impairment, it is considered to be in a labile, nonconsolidated state, and if it is insensitive to administration of these amnesic treatments, then the memory is, by definition, consolidated (Dudai, 2004; McGaugh, 1966). Once a memory has become consolidated, it remains in the fixed state.

Consolidation theory became the central tenet around which the field of systems neuroscience of memory has evolved. Since that time, the field has enjoyed numerous successes in creating models at different levels of analysis to describe the changes that occur when a memory is converted from labile trace to a “fixed” one. These include long-term potentiation (Bliss & Lomo, 1973; Martin et al., 2000) and the identification of transcription factors that act as gateways to LTM (Bourtchuladze et al., 1994; Dash, Hochner, & Kandel, 1990; Kandel, 2001; Yin et al., 1994).

Since its inception, there have been some challenges to consolidation theo...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Contributors
• Chapter 1. The Discovery of Memory Reconsolidation
• Chapter two. The Dynamic Nature of Memory
• Chapter 3. Mechanisms and Functions of Hippocampal Memory Reconsolidation
• Chapter four. Reconsolidation of Pavlovian Conditioned Defense Responses in the Amygdala
• Chapter five. Memory Reconsolidation: Lingering Consolidation and the Dynamic Memory Trace
• Chapter six. Memory Reconsolidation Versus Extinction
• Chapter seven. Memory Reconsolidation and Extinction in Invertebrates: Evolutionarily Conserved Characteristics of Memory Reprocessing and Restabilization
• Chapter eight. Using Reconsolidation and Extinction to Weaken Fear Memories in Animal Models
• Chapter 9. Reconsolidation in Humans
• Chapter ten. Reconsolidation of Declarative Memory
• Chapter eleven. Episodic Memory Reconsolidation: An Update
• Chapter 12. Disrupting Consolidation and Reconsolidation of Human Emotional Memory with Propranolol: A Meta-Analysis
• Chapter 13. The Translational Potential of Memory Reconsolidation
• Chapter 14. Memory Reconsolidation, Trace Reassociation and the Freudian Unconscious
• Index