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.

No abstract

Hippocampus is hypothesized to play a temporary role in the retrieval of context memories. Similarly, previous studies have reported that the expression of context memories becomes more generalized as memory ages. We report, first, that contextual fear memory expression changes from being sensitive to dorsal hippocampus inactivation by muscimol at 2 days post-conditioning, to insensitive at 28 days, and second, that over the same period rats lose their ability to discriminate between a novel and conditioned context. Furthermore, we show that repeated brief memory reactivation sessions prevent memory from becoming both hippocampus-independent and generalized.

In the past decades, the cellular and molecular mechanisms underlying memory consolidation, reconsolidation, and extinction have been well characterized. However, the neurobiological underpinnings of forgetting processes remain to be elucidated. Here we used behavioral, pharmacological and electrophysiological approaches to explore mechanisms controlling forgetting. We found that post-acquisition chronic inhibition of the N-methyl-D-aspartate receptor (NMDAR), L-type voltage-dependent Ca2+ channel (LVDCC), and protein phosphatase calcineurin (CaN), maintains long-term object location memory that otherwise would have been forgotten. We further show that NMDAR activation is necessary to induce forgetting of object recognition memory. Studying the role of NMDAR activation in the decay of the early phase of long-term potentiation (E-LTP) in the hippocampus, we found that ifenprodil infused 30 min after LTP induction in vivo blocks the decay of CA1-evoked postsynaptic plasticity, suggesting that GluN2B-containing NMDARs activation are critical to promote LTP decay. Taken together, these findings indicate that a well-regulated forgetting process, initiated by Ca2+ influx through LVDCCs and GluN2B-NMDARs followed by CaN activation, controls the maintenance of hippocampal LTP and long-term memories over time.

Some memories enter into a labile state after retrieval, requiring reconsolidation in order to persist. One functional role of memory reconsolidation is the updating of existing memories. There are reports suggesting that reconsolidation can be modulated by a particular endogenous process taking place concomitantly to its natural course, such as water or sleep deprivation. Here, we investigated whether an endogenous process activated during a natural/physiological experience, or a pharmacological intervention, can also contribute to memory content updating. Using the contextual fear conditioning paradigm in rats, we found that the endogenous content of an aversive memory can be updated during its reconsolidation incorporating consequences of natural events such as water deprivation, transforming a previously stored memory into a state-dependent one. This updating seems to be mediated by the activation of angiotensin AT1 receptors in the dorsal hippocampus and local infusion of human angiotensin II (ANGII) was shown to mimic the water deprivation effects on memory reconsolidation. Systemic morphine injection was also able to turn a previously acquired experience into a state-dependent memory, reproducing the very same effects obtained by water deprivation or local angiotensin II infusion, and suggesting that other state-dependent-inducing protocols would also be able to contribute to memory updating. These findings trigger new insights about the influence of ordinary daily life events upon memory in its continuing reconstruction, adding the realm of reconsolidation to the classical view of endogenous modulation of consolidation.