Amnesia or retrieval deficit? Implications of a molecular approach to the question of reconsolidation

Miller, Courtney A.; Sweatt, J. David

doi:10.1101/lm.304606

Cited by 53 publications

(30 citation statements)

References 80 publications

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“…Indeed, one could argue that inhibition of protein synthesis after nonreinforced reactivation could hinder future retention not by deleting the trace or impairing its expression but by affecting an active protein synthesis-dependent process initiated at the moment of retrieval and necessary to access or find the information needed to build up a suitable behavioral representation. In this respect, the existence of extinction savings after the recovery of IA memory induced by ANI and the need of protein synthesis for extinction of the recovered avoidance response indicate that reconsolidation blockade does not fully erase extinction memory but, instead, hinders restabilization of, or access to, information necessary for remembering it (34,46).…”

Section: Discussionmentioning

confidence: 99%

Retrieval induces reconsolidation of fear extinction memory

Rossato

Bevilaqua

Izquierdo

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The nonreinforced expression of long-tem memory may lead to two opposite protein synthesis-dependent processes: extinction and reconsolidation. Extinction weakens consolidated memories, whereas reconsolidation allows incorporation of additional information into them. Knowledge about these two processes has accumulated in recent years, but their possible interaction has not been evaluated yet. Here, we report that inhibition of protein synthesis in the CA1 region of the dorsal hippocampus after retrieval of fear extinction impedes subsequent reactivation of the extinction memory trace without affecting its storage or that of the initial fear memory. Our results suggest that extinction memory is susceptible to a retrieval-induced process similar to reconsolidation in the hippocampus.learning | anisomycin | amnesia W ithout retrieval, memories would be unusable. Retrieval, however, can weaken long-term memory (LTM). In fact, it is known that reactivation through exposure to training-related stimuli transiently destabilizes the consolidated memory trace, which, to remain behaviorally available, must go through a protein synthesis-dependent process called reconsolidation. Additionally, when retrieval in the absence of appropriate reinforcement is repeated regularly enough, it induces memory extinction, a phenomenon characterized by a decrease in the amplitude and/or frequency of the learned response that also requires protein synthesis in definite areas of the brain.Reconsolidation and extinction are functionally related; both require acquisition of retrieval-related information connected to previous learning. They are mechanistically different, however; extinction involves additional learning and replaces the expression of the original memory with a newly formed one (1, 2), whereas reconsolidation restabilizes the old memory opened to modification or strengthening by retrieval (3-6).Given the clinical relevance that reconsolidation blockade and extinction enhancement could have (7,8), research about the consequences of retrieval on LTM persistence has concentrated on the molecular, neuroanatomical, and electrophysiological requirements of reconsolidation and extinction (9-12) as well as on the elucidation of the behavioral and neurochemical conditions that constrain or facilitate either process (13-15). The potential interaction of extinction and reconsolidation has been comparatively less studied, and when so, the studies produced contradictory results. Thus, it was earlier proposed that extinction can act as a boundary condition preventing fear memories from undergoing reconsolidation (16,17), but more recent reports indicate that reconsolidation is independent of any influence from fear extinction (18). Indeed, the likelihood of reconsolidation for fear extinction memory has never been evaluated before.To do that, we analyzed the effect of the intrahippocampal administration of protein synthesis inhibitors on the stability of a consolidated fear extinction memory trace. Our findings strongly support the hypothesi...

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Section: Discussionmentioning

confidence: 99%

Retrieval induces reconsolidation of fear extinction memory

Rossato

Bevilaqua

Izquierdo

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Here, we present evidence that retrieval induces NF-Bdependent neural plasticity in hippocampus, which is required for long-term memory restabilization. These data shed light on how information is processed and which brain areas are involved in the distinct phases of memory storage, establishing a correlation between specific molecular events and the behavioral readout (Miller and Sweatt, 2006).…”

Section: Discussionmentioning

confidence: 99%

Activation of Hippocampal Nuclear Factor-κB by Retrieval Is Required for Memory Reconsolidation

Boccia¹,

Freudenthal²,

Blake³

et al. 2007

J. Neurosci.

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Initially, memory is labile and requires consolidation to become stable. However, several studies support that consolidated memories can undergo a new period of lability after retrieval. The mechanistic differences of this process, termed reconsolidation, with the consolidation process are under debate, including the participation of hippocampus. Up to this point, few reports describe molecular changes and, in particular, transcription factor (TF) involvement in memory restabilization. Increasing evidence supports the participation of the TF nuclear factor-B (NF-B) in memory consolidation. Here, we demonstrate that the inhibition of NF-B after memory reactivation impairs retention of a hippocampal-dependent inhibitory avoidance task in mice. We used two independent disruptive strategies to reach this conclusion. First, we administered intracerebroventricular or intrahippocampal sulfasalazine, an inhibitor of IKK (IB kinase), the kinase that activates NF-B. Second, we infused intracerebroventricular or intrahippocampal B decoy, a direct inhibitor of NF-B consisting of a double-stranded DNA oligonucleotide that contains the B consensus sequence. When injected immediately after memory retrieval, sulfasalazine or B decoy (Decoy) impaired long-term retention. In contrast, a one base mutated B decoy (mDecoy) had no effect. Furthermore, we also found NF-B activation in the hippocampus, with a peak 15 min after memory retrieval. This activation was earlier than that found during consolidation. Together, these results indicate that NF-B is an important transcriptional regulator in memory consolidation and reconsolidation in hippocampus, although the temporal kinetics of activation differs between the two processes.

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“…In general, the same principles apply to both consolidation and reconsolidation studies. However, as memory reconsolidation is less well understood, additional questions need to be addressed in relation to the type of proteins involved, the temporal duration and the rate of protein synthesis required (Alberini, 2005;Alberini, 2007;Dudai, 2004;Gold, 2006;Lattal & Abel 2004;Miller & Sweatt 2006;Rudy et al, 2006). Importantly, the effect of protein synthesis inhibition after memory reactivation is likely to be more complex, and, in fact, it needs to take into account other aspects that involve additional phases of protein synthesis, such as the fact that consolidation has in part already occurred and the possible additional implicit nature of reactivation experiences (Anokhin et al, 2002;Alberini, 2007).…”

Section: Requirement For Protein Synthesis During Memory Formation: Tmentioning

confidence: 99%

The role of protein synthesis during the labile phases of memory: Revisiting the skepticism

Alberini

2008

Neurobiology of Learning and Memory

159

111

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Despite the fact that extensive evidence supports the view that phases of de novo protein synthesis are necessary for memory formation and maintenance, doubts are still raised. Skeptics generally argue that amnesia and the disruption of long-term synaptic plasticity are caused by "non-specific effects" of the reagents or approaches used to disrupt protein synthesis. This paper attempts to clarify some of these issues by reviewing, discussing and providing results addressing some of the major critiques that argue against the idea that de novo protein synthesis is necessary for the stabilization of long-term memory.

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Amnesia or retrieval deficit? Implications of a molecular approach to the question of reconsolidation

Cited by 53 publications

References 80 publications

Retrieval induces reconsolidation of fear extinction memory

Retrieval induces reconsolidation of fear extinction memory

Activation of Hippocampal Nuclear Factor-κB by Retrieval Is Required for Memory Reconsolidation

The role of protein synthesis during the labile phases of memory: Revisiting the skepticism

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