Social interaction-induced fear memory reduction: exploring the influence of dopamine and oxytocin receptors on memory updating.

It has been well established that a consolidated memory can be updated during the plastic state induced by reactivation. This updating process opens the possibility to modify maladaptive memory. In the present study, we evaluated whether fear memory could be updated to less-aversive level by incorporating hedonic information during reactivation.

PARP1 in the intersection of different DNA repair pathways, memory formation, and sleep pressure in neurons.

Poly(ADP-ribose) polymerase-1 (PARP1) is a bottleneck that connects different DNA pathways during a DNA damage response. Interestingly, PARP1 has a dualist role in neurons, acting as a neuroprotector and inducer of cell death in distinct neurological diseases. Recent studies significantly expanded our knowledge of how PARP1 regulates repair pathways in neurons and uncovered new roles for PARP1 in promoting sleep to enhance DNA repair.

Molecular mechanisms underpinning deconditioning-update in fear memory.

Traumatic experiences are closely associated with some psychiatric conditions such as post-traumatic stress disorder. Deconditioning-update promotes robust and long-lasting attenuation of aversive memories. The deconditioning protocol consists of applying weak/neutral footshocks during reactivations, so that the original tone-shock association is replaced by an innocuous stimulus that does not produce significant fear response.

Characterization of deconditioning-update on fear memory attenuation.

Fear memory expression can be attenuated by updating the footshock perception during the plastic state induced by retrieval, from a strong unconditioned stimulus to a very weak one through deconditioning. In this process, the original fear association of the conditioned stimulus with the footshock is substituted by an innocuous stimulus and the animals no longer express a fear response. In the present study, we explore the boundaries of this deconditioning-update strategy by the characterization of this phenomenon.

Re-exposures in the Dark Cycle Promote Attenuation of Fear Memory: Role of the Circadian Cycle and Glucocorticoids.

It has been shown that a previously consolidated memory can incorporate either new external information or a novel internal emotional state following a labile state induced by retrieval. This updating process allows editing unwanted fear memory, leading to the reduction of the fear response. Memory can be modulated by the circadian cycle.

Effects of hippocampal IPR inhibition on contextual fear memory consolidation, retrieval, reconsolidation and extinction.

Intracellular calcium stores (ICS) play a dynamic role in neuronal calcium (Ca) homeostasis both by buffering Ca excess in the cytoplasm or providing an additional source of Ca when concentration increase is needed. However, in spite of the large body of evidence showing Ca as an essential second messenger in many signaling cascades underlying synaptic plasticity, the direct involvement of the intracellular Ca-release channels (ICRCs) in memory processing has been highly overlooked. Here we investigated the role of the ICRC inositol 1,4,5-trisphosphate receptor (IPR) activity during different memory phases using pharmacological inhibition in the dorsal hippocampus during contextual fear conditioning.

Adolescent female rats undergo full systems consolidation of an aversive memory, while males of the same age fail to discriminate contexts.

Generalization is an adaptive process that allows animals to deal with threatening circumstances similar to prior experiences. Systems consolidation is a time-dependent process in which memory loses it precision concomitantly with reorganizational changes in the brain structures that support memory retrieval. In this, memory becomes progressively independent from the hippocampus and more reliant on cortical structures.

Systems consolidation and fear memory generalisation as a potential target for trauma-related disorders.

Fear memory generalisation is a central hallmark in the broad range of anxiety and trauma-related disorders. Recent findings suggest that fear generalisation is closely related to hippocampal dependency during retrieval. In this review, we describe the current understanding about memory generalisation and its potential influence in fear attenuation through pharmacological and behavioural interventions.

Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory.

-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones.

Understanding the dynamic and destiny of memories.

Memory formation enables the retention of life experiences overtime. Based on previously acquired information, organisms can anticipate future events and adjust their behaviors to maximize survival. However, in an ever-changing environment, a memory needs to be malleable to maintain its relevance.

Effect of the Endocannabinoid System in Memory Updating and Forgetting.

Most memories of life experiences will be forgotten or modified over time. Although several studies have investigated the processes underlying memory formation, the mechanisms behind memory updating and forgetting remain unclear. The endocannabinoid system has been shown to be closely involved in various memory processes such as consolidation, destabilization, and extinction.

LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing.

Long-term memory has been associated with morphological changes in the brain, which in turn tightly correlate with changes in synaptic efficacy. Such plasticity is proposed to rely on dendritic spines as a neuronal canvas on which these changes can occur. Given the key role of actin cytoskeleton dynamics in spine morphology, major regulating factors of this process such as Cofilin 1 (Cfl1) and LIM kinase (LIMK), an inhibitor of Cfl1 activity, are prime molecular targets that may regulate dendritic plasticity.

Rewarding information presented during reactivation attenuates fear memory: Methylphenidate and fear memory updating.

In the last decade it became clear that a previously consolidated memory can be modified during the plastic state induced by retrieval. This updating process opens the possibility to adapt undesired memory. Here we investigated whether fear memory could be updated to less-aversive/positive level by inserting hedonic information during retrieval.

Shifting from fear to safety through deconditioning-update.

Aversive memories are at the heart of psychiatric disorders such as phobias and post-traumatic stress disorder (PTSD). Here, we present a new behavioral approach in rats that robustly attenuates aversive memories. This method consists of 'deconditioning' animals previously trained to associate a tone with a strong footshock by replacing it with a much weaker one during memory retrieval.

Hippocampal HECT E3 ligase inhibition facilitates consolidation, retrieval, and reconsolidation, and inhibits extinction of contextual fear memory.

Ubiquitination is involved in synaptic plasticity and memory, but the involvement of HECT E3 ligases in these processes has not yet been established. Here, we bilaterally infused heclin, a specific inhibitor of some of these ligases, into the dorsal hippocampus of male Wistar rats that were trained in a contextual fear conditioning. Heclin improved short-term memory, consolidation, retrieval, and reconsolidation when administered immediately post training, prior to testing, or after memory reactivation, respectively.

Chronic fluoxetine prevents fear memory generalization and enhances subsequent extinction by remodeling hippocampal dendritic spines and slowing down systems consolidation.

Fear memory overgeneralization contributes to the genesis and persistence of anxiety disorders and is a central hallmark in the pathophysiology of post-traumatic stress disorder (PTSD). Recent findings suggest that fear generalization is closely related to hippocampal dependency during retrieval. The selective serotonin reuptake inhibitor (SSRI) fluoxetine has been used as a first-line treatment for PTSD; however, how it exerts its therapeutic effect remains a matter of debate.

Role of calcium-permeable AMPA receptors in memory consolidation, retrieval and updating.

The role of the calcium-permeable AMPA receptor (CP-AMPAR) in synaptic plasticity is well established. CP-AMPAR is believed to be recruited to synapse when the memory trace is in a plastic state; however, the direct implications of its expression for memory processes is less known. Here, we investigated the contribution of CP-AMPAR expressed in the basolateral amygdala (BLA) and hippocampus (HPC) in consolidation of different types of memory, retrieval and memory update.

Author Correction: Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats.

In the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation. However, most of the pharmacological agents used in preclinical studies cannot be administered to humans. Caffeine is one of the world's most popular psychoactive drugs and its effects on cognitive and mood states are well documented.

Calpain modulates fear memory consolidation, retrieval and reconsolidation in the hippocampus.

It has been proposed that long-lasting changes in dendritic spines provide a physical correlate for memory formation and maintenance. Spine size and shape are highly plastic, controlled by actin polymerization/depolymerization cycles. This actin dynamics are regulated by proteins such as calpain, a calcium-dependent cysteine protease that cleaves the structural cytoskeleton proteins and other targets involved in synaptic plasticity.

Synaptic consolidation as a temporally variable process: Uncovering the parameters modulating its time-course.

Memories are not instantly created in the brain, requiring a gradual stabilization process called consolidation to be stored and persist in a long-lasting manner. However, little is known whether this time-dependent process is dynamic or static, and the factors that might modulate it. Here, we hypothesized that the time-course of consolidation could be affected by specific learning parameters, changing the time window where memory is susceptible to retroactive interference.

Hippocampal plasticity mechanisms mediating experience-dependent learning change over time.

The requirement of NMDA receptor (NMDAR) activity for memory formation is well described. However, the plasticity mechanisms for memory can be modified by experience, such that a future similar learning becomes independent of NMDARs. This effect has often been reported in learning events conducted with a few days interval.