Reconsolidation Allows Fear Memory to Be Updated to a Less Aversive Level through the Incorporation of Appetitive Information

Abstract

The capacity to adapt to new situations is one of the most important features of memory. When retrieved, memories may undergo a labile state that is sensitive to modification. This process, called reconsolidation, can lead to memory updating through the integration of new information into a previously consolidated memory background. Thus reconsolidation provides the opportunity to modify an undesired fear memory by updating its emotional valence to a less aversive level. Here we evaluated whether a fear memory can be reinterpreted by the concomitant presentation of an appetitive stimulus during its reactivation, hindering fear expression. We found that memory reactivation in the presence of appetitive stimuli resulted in the suppression of a fear response. In addition, fear expression was not amenable to reinstatement, spontaneous recovery, or rapid reacquisition. Such effect was prevented by either systemic injection of nimodipine or intra-hippocampal infusion of ifenprodil, indicating that memory updating was mediated by a reconsolidation mechanism relying on hippocampal neuronal plasticity. Taken together, this study shows that reconsolidation allows for a 're-signification' of unwanted fear memories through the incorporation of appetitive information. It brings a new promising cognitive approach to treat fear-related disorders.

An appetitive experience after fear memory destabilization attenuates fear retention: involvement GluN2B-NMDA receptors in the Basolateral Amygdala Complex

“…This pattern is coherent with previous results from our laboratory (Piñeyro et al 2014) and with others that indicate the critical importance of memory destabilization in order to be able to affect memory traces, both in rodents (Lee et al 2008) and humans (Sevenster et al 2012(Sevenster et al , 2013. Haubrich et al (2015) and the present findings revealed that those reactivation sessions that were unable to destabilize the fear memory preclude the influence of the appetitive experience. Moreover, there is agreement regarding the pivotal role of the GluN2B subunit of the NMDA receptor in the BLA in fear memory destabilization (Ben Mamou et al 2006;Wang et al 2009;Milton et al 2013).…”

“…Olshavsky et al (2013) found that pairing a previously appetitive CS with foot shocks retarded later reacquisition of the appetitive response. Haubrich et al (2015) recently demonstrated that when a fearconditioned context was reassociated with the presence of appetitive food, the conditioned fear response was substantially reduced. Finally, in an elegant and ground-breaking paper using optogenetic techniques to directly activate neurons involved in memory acquisition, Redondo et al (2014) bidirectionally changed the hedonic value of both appetitive and aversive memories.…”

The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction

“…During reconsolidation, memories may return to a transitory labile state sensitive to modifications (Nader et al 2000;Haubrich et al 2015), and it happens when the animal is reexposed briefly to the training environment. If this exposure takes longer in the absence of the unconditioned stimulus, extinction takes place, resulting in a new learning that is temporarily effective in inhibiting the conditioned response (Pavlov 1927;Quirk and Mueller 2008).…”

“…During reconsolidation, memories can return to a transitory labile state that is sensitive to modifications (Nader et al 2000;Haubrich et al 2015). Since we found that AM251 increased freezing levels while the CP55940 was amnestic when administered immediately after memory reactivation, we suggest that RSC-CB1Rs inhibit contextual fear memory reconsolidation.…”

“…Then, animals were bilaterally infused intra-RSC with either CP55940 or vehicle 20 min before the extinction session. One day later, they were subjected to reinstatement (a single 0.5-mA footshock in a different environment, according to Haubrich et al 2015). In the following day, they were tested (Fig.…”