Retrieval induces reconsolidation of fear extinction memory

Abstract

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...

Treatment of fear memories: interactions between extinction and reconsolidation

“…Each of these brain areas is specifically involved both in the consolidation and in the extinction of the respective behaviors. This suggests the possibility of yet another form of improving the extinction of fear memories indicates an important behavioral property of extinction that had not been previously described (Rossato et al 2010), and is in line with the procedures advocated by Monfils et al (2009) and Schiller et al (2010) for the inhibition of the recall of fear.…”

“…Recently, García de la Torre et al (2010) and Rossato et al (2010) reported that extinction itself, being one form of learning, can be subjected to reconsolidation in at least two different tasks in rats. Both groups showed that the infusion of anisomycin into selected brain structures right after the first extinction trial of a series hindered extinction performance in subsequent trials.…”

“…García de la Torre et al (2010) studied conditioned taste aversion and infused the protein synthesis inhibitor into the insular cortex. Rossato et al (2010) studied inhibitory avoidance and infused the anisomycin into the dorsal hippocampus. Each of these brain areas is specifically involved both in the consolidation and in the extinction of the respective behaviors.…”

Methyl‐donor deficiency in adolescence affects memory and epigenetic status in the mouse hippocampus

“…It has been revealed that sufficient consolidation of fear extinction is capable of preventing spontaneous recovery. For example, one study using an avoidance task showed that a 5‐day extinction paradigm prevented the spontaneous recovery of fear in male rats (Matsuda et al ; Rossato et al ). Recovery of extinguished fear was reduced with the administration of d ‐cycloserine, a partial NMDA receptor agonist, which is considered to play an enhancing role on the consolidation of fear extinction memory (Myers & Carlezon ; Vervliet ).…”

Memory reconsolidation allows the consolidation of a concomitant weak learning through a synaptic tagging and capture mechanism

“…CHX (20 μg/side, 20 μg/μl, or 2.2 mg/kg, 2.2 mg/ml) and AP5 (5 μg/side, 5 μg/μl) were diluted in dimethyl sulfoxide (DMSO) 1% and phosphate buffered saline (PBS) respectively, and infused locally in the CA1 region of the dorsal hippocampus (1 μl/side) or i.p. (1 ml/kg) (Rossato et al, ; Moncada et al, ).…”