Reconsolidation: the advantage of being refocused
Introduction
Even newcomers to the field of memory consolidation quickly observe that the debate on reconsolidation (see glossary) is not at all that new. Yet, they also realize that novelty is not a prerequisite for genuine excitement. The debate on whether items in long-term memory are consolidated just once per item shortly after their encoding or regain upon their reactivation renewed sensitivity to amnestic agents is as emotional as it used to be 40 years ago, and perhaps now even more so. In recent years this revitalized dispute has triggered a surge of publications on reconsolidation. Within less than a decade, the average publication rate of the reconsolidation community has increased over 50 fold, and is now approaching the alarming rate of one paper per week. The only solace offered to the potentially alarmed reader is that the ratio of reviews to original research papers is rather high, meaning that the level of novelty to be digested is acceptable.
Admittedly, the present discussion could tilt the balance even further in favor of the polemics versus the data. As a pre-emptive measure, this treatment of the literature is kept minimal (for a review of the field up until its renaissance in 2000, see Sara [1]; for the influential harbinger of that renaissance, see Nader et al. [2]; for coverage of the literature up to 2004, see Dudai [3] and Alberini [4]). Here, I promote the following viewpoints. First, reconsolidation studies, which seemed to wave proudly an anti-paradigmatic revolutionary flag, now risk becoming another scientific paradigm, which, unless shaken a bit at the outset, will inevitably end up stagnating till a new revolution erupts. Second, in attempting to understand reconsolidation, quite a number of contemporary studies employ similar approaches to those used 40 years ago, and, therefore, they are bound to yield similar answers, or lack of answers. Third, the conceptual focus of research in this field, which is to construe reconsolidation in the framework of consolidation, blurs a potentially more rewarding goal. This goal is to contribute to the understanding of memory persistence and retrieval, of which we know so little, but without which memory will never be understood.
Section snippets
Reconsolidation is generalized to many experimental systems and protocols
Reconsolidation is no longer considered by many as an eccentric phenomenon that can be detected in a few systems only during certain hours of the day. Data accumulated during the past few years have extended significantly the number of memory systems and protocols that display reconsolidation. These now include invertebrates and vertebrates, simple and complex learning, and aversive and reward conditioning (for a selection of recent examples of species and protocols, see [5, 6, 7, 8, 9, 10, 11••
Reconsolidation, however, might not be universal
Whereas consolidation has, to date, been detected in every type and instance of long-term memory formation [3], in the case of reconsolidation the situation seems to be different (e.g. [17]; for a review of earlier reports that failed to find reconsolidation, see Dudai [3]). In certain systems reconsolidation could not be detected, and in others, conditions have been observed in which the phenomenon disappears. This has led to the notion that there are boundary conditions for reconsolidation [18
Reconsolidation is not re-consolidation
Further evidence has been accumulated in recent years concerning the involvement in reconsolidation of identified membrane receptors, downstream signal transduction cascades and transcription factors, subsets of protein synthesis dependent mechanisms and identified neuronal circuits [10, 13, 15, 16••, 19, 20, 21, 22, 23••, 24, 25••, 26]. Of special interest are those studies that further differentiate the molecular and circuit mechanisms of reconsolidation from those of consolidation, and that
Blockade of reconsolidation is not facilitated extinction
Multiple lines of evidence also now exist to refute the possibility that the amnesia following blockade of reconsolidation (post-reconsolidation amnesia) is only an enhanced experimental extinction (see glossary) of the original memory. This evidence is based on behavioral, anatomical and molecular studies. In the case of fear conditioning in the rat, post-reconsolidation amnesia was shown to lack the typical behavioral attributes of extinction, including context-dependent renewal, spontaneous
Reconsolidation entails not only risks to the reactivated memory but also gains
In the majority of experiments on reconsolidation, amnestic agents are used to identify the phenomenon. However, recent reports have augmented the view, expressed earlier [1], that reconsolidation might also provide a window of opportunity for the strengthening of the memory trace [6, 25••]. Of particular interest in this context is the recent report that activation of amygdalar protein kinase A (PKA), a key component of the synaptic plasticity machinery, was sufficient to enhance fear memory
Is reconsolidation an updating mechanism?
A more generalized interpretation of the aforementioned data is that reconsolidation is a manifestation of a memory updating mechanism, that is, adapting the reactivated memory to the new circumstances. This idea has been around in the field for some time now [1, 3, 32]. Recent data on this are, however, conflicting. In the case of long-term taste memory in the insular cortex of the rat, post-retrieval intracortical blockade of protein synthesis disrupted memory only if the experience was
Boundary conditions of reconsolidation
To date, several conditions have been proposed to constrain reconsolidation. The first is trace dominance, that is, the ability of the association to control behavior after retrieval [28]. As noted above, in several systems, if the trace extinguishes, the extinction trace, which hence controls behavior, rather than the original trace which does not, becomes transiently sensitive to the amnestic agents [28, 29, 35]. The second is the age of memory; in some systems, older memories become less
Promising clinical applications
The potential for exploiting reconsolidation for therapeutic purposes is a major incentive in this field, and the attempts to harness this phenomenon for clinical use progress in parallel with the attempts to understand what the phenomenon really means. First and foremost, there are ongoing attempts to use reconsolidation to ameliorate post-traumatic stress disorder (PTSD). One method that has been explored involves administration of a beta adrenergic blocker as a potential post-reconsolidation
Interim summary: what reconsolidation is, and what it is not
Recent developments in the field can be combined with earlier findings to support the following heuristic conclusions:
- 1.
Reconsolidation is a temporarily altered state of the memory trace following memory reactivation. This altered state is characterized by increased sensitivity to amnestic agents, such as inhibitors of macromolecular synthesis, possibly because of enhanced plasticity of the neuronal circuit that encodes the memory trace or parts of it.
- 2.
Reconsolidation is widespread but possibly
A shift in focus is needed
The field of reconsolidation is a victim of its own history. This is felt in both the conceptual and the methodological areas. It is consistently evaluated in the context of a conceptual framework of the dual-trace hypothesis (see glossary), which assumes the existence of memory phases (short and fleeting, long and stable), and in the context of consolidation, which converts the ephemeral trace into the seemingly secure world of engrams. This situation might prove to be a far from optimal
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Glossary
- Amnestic agents
- Chemical or physical agents, such as inhibitors of protein synthesis, electroconvulsive shock, or distracting sensory stimuli, that cause amnesia if applied before consolidation is completed.
- Dual-trace hypothesis
- The hypothesis that memory items exist in two consecutive states, the first short-term and unstable, the second long-term and relatively stable.
- Experimental extinction (alias extinction)
- The decline in the frequency or intensity of a learned response following the
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Temporary address: Center for Neural Science, New York University, New York, NY 10003, USA.