Persistence Of Memory Research Articles

The late consolidation of an aversive memory is promoted by VTA dopamine release in the dorsal hippocampus

The hippocampus has been implicated in the processing and storage of aversive memories but the precise mechanisms by which these memories persist in time remain elusive. We have demonstrated that dopaminergic neurotransmission in the dorsal hippocampus regulates the long-term storage of both appetitive and aversive memories at a critical time point known as "late consolidation" (12hr after the learning experience). This modulation appears to have opposite effects depending on the valence of the stimuli, with hippocampal dopamine release peaking immediately and 13-17hr after a rewarding experience. Here, we determined the release pattern of hippocampal dopamine following an aversive experience, in order to better understand this opposite modulation process. We observed significant increases in dopamine levels at several times (6-8, 11-12, and 15hr) after subjecting rats to a conditioned place aversion (CPA) task with the aversive agent lithium chloride (LiCl). Early pharmacological blockade of hippocampal DA receptors impaired CPA memory consolidation. In addition and consistent with previous findings showing that late post-training infusions of dopaminergic agents into the hippocampus modulate the long-term storage of aversive memories, we found that the photostimulation of dopaminergic VTA fibers in the dorsal hippocampus 11-12hr after CPA training was enough to transform a short-lasting long-term memory into a long-lasting one. The fact that the persistence of an aversive memory can still be affected several hours after the learning experience opens new avenues to develop behavioral and pharmacological strategies for the treatment of a variety of mental disorders.

Hepatitis A vaccination and its immunological and epidemiological long-term effects – a review of the evidence

ABSTRACT Hepatitis A virus (HAV) infections continue to represent a significant disease burden causing approximately 200 million infections, 30 million symptomatic illnesses and 30,000 deaths each year. Effective and safe hepatitis A vaccines have been available since the early 1990s. Initially developed for individual prophylaxis, HAV vaccines are now increasingly used to control hepatitis A in endemic areas. The human enteral HAV is eradicable in principle, however, HAV eradication is currently not being pursued. Inactivated HAV vaccines are safe and, after two doses, elicit seroprotection in healthy children, adolescents, and young adults for an estimated 30–40 years, if not lifelong, with no need for a later second booster. The long-term effects of the single-dose live-attenuated HAV vaccines are less well documented but available data suggest they are safe and provide long-lasting immunity and protection. A universal mass vaccination strategy (UMV) based on two doses of inactivated vaccine is commonly implemented in endemic countries and eliminates clinical hepatitis A disease in toddlers within a few years. Consequently, older age groups also benefit due to the herd protection effects. Single-dose UMV programs have shown promising outcomes but need to be monitored for many more years in order to document an effective immune memory persistence. In non-endemic countries, prevention efforts need to focus on ‘new’ risk groups, such as men having sex with men, prisoners, the homeless, and families visiting friends and relatives in endemic countries. This narrative review presents the current evidence regarding the immunological and epidemiological long-term effects of the hepatitis A vaccination and finally discusses emerging issues and areas for research.

The relationship between hippocampal subfield volumes and autobiographical memory persistence.

Structural integrity of the human hippocampus is widely acknowledged to be necessary for the successful encoding and retrieval of autobiographical memories. However, evidence for an association between hippocampal volume and the ability to recall such memories in healthy individuals is mixed. Here we examined this issue further by combining two approaches. First, we focused on the anatomically distinct subregions of the hippocampus where more nuanced associations may be expressed compared to considering the whole hippocampal volume. A manual segmentation protocol of hippocampal subregions allowed us to separately calculate the volumes of the dentate gyrus/CA4, CA3/2, CA1, subiculum, pre/parasubiculum and uncus. Second, a critical feature of autobiographical memories is that they can span long time periods, and so we sought to consider how memory details persist over time by conducting a longitudinal study whereby participants had to recall the same autobiographical memories on two visits spaced 8 months apart. Overall, we found that there was no difference in the total number of internal (episodic) details produced at Visits 1 and 2. However, further probing of detail subcategories revealed that specifically the amount of subjective thoughts and emotions included during recall had declined significantly by the second visit. We also observed a strong correlation between left pre/parasubiculum volume and the amount of autobiographical memory internal details produced over time. This positive relationship was evident for particular facets of the memories, with remembered events, perceptual observations and thoughts and emotions benefitting from greater volume of the left pre/parasubiculum. These preliminary findings expand upon existing functional neuroimaging evidence by highlighting a potential link between left pre/parasubiculum volume and autobiographical memory. A larger pre/parasubiculum appears not only to protect against memory decay, but may possibly enhance memory persistence, inviting further scrutiny of the role of this brain region in remote autobiographical memory retrieval.

MTOR inhibition impairs extinction memory reconsolidation

Fear-motivated avoidance extinction memory is prone to hippocampal brain-derived neurotrophic factor (BDNF)-dependent reconsolidation upon recall. Here, we show that extinction memory recall activates mammalian target of rapamycin (mTOR) in dorsal CA1, and that post-recall inhibition of this kinase hinders avoidance extinction memory persistence and recovers the learned aversive response. Importantly, coadministration of recombinant BDNF impedes the behavioral effect of hippocampal mTOR inhibition. Our results demonstrate that mTOR signaling is necessary for fear-motivated avoidance extinction memory reconsolidation and suggests that BDNF acts downstream mTOR in a protein synthesis-independent manner to maintain the reactivated extinction memory trace.

Phenotypes to remember: Evolutionary developmental memory capacity and robustness.

There is increased awareness of the possibility of developmental memories resulting from evolutionary learning. Genetic regulatory and neural networks can be modelled by analogous formalism raising the important question of productive analogies in principles, processes and performance. We investigate the formation and persistence of various developmental memories of past phenotypes asking how the number of remembered past phenotypes scales with network size, to what extent memories stored form by Hebbian-like rules, and how robust these developmental "devo-engrams" are against networks perturbations (graceful degradation). The analogy between neural and genetic regulatory networks is not superficial in that it allows knowledge transfer between fields that used to be developed separately from each other. Known examples of spectacular phenotypic radiations could partly be accounted for in such terms.

The singing voice is special: Persistence of superior memory for vocal melodies despite vocal-motor distractions

Vocal melodies sung without lyrics (la la) are remembered better than instrumental melodies. What causes the advantage? One possibility is that vocal music elicits subvocal imitation, which could promote enhanced motor representations of a melody. If this motor interpretation is correct, distracting the motor system during encoding should reduce the memory advantage for vocal over piano melodies. In Experiment 1, participants carried out movements of the mouth (i.e., chew gum) or hand (i.e., squeeze a beanbag) while listening to 24 unfamiliar folk melodies (half vocal, half piano). In a subsequent memory test, they rated the same melodies and 24 timbre-matched foils from ‘1–Definitely New’ to ‘7–Definitely Old’. There was a memory advantage for vocal over piano melodies with no effect of group and no interaction. In Experiment 2, participants carried out motor activities during encoding more closely related to singing, either silently articulating (la la) or vocalizing without articulating (humming continuously). Once again, there was a significant advantage for vocal melodies with no effect or interaction of group. In Experiment 3, participants audibly whispered (la la) repeatedly during encoding. Again, the voice advantage was present and did not differ appreciably from prior research with no motor task during encoding. However, we observed that the spontaneous phase-locking of whisper rate and musical beat tended to predict enhanced memory for vocal melodies. Altogether the results challenge the notion that subvocal rehearsal of the melody drives enhanced memory for vocal melodies. Instead, the voice may enhance engagement.

The effects of lithium chloride and cathodal/anodal transcranial direct current stimulation on conditional fear memory changes and the level of p-mTOR/mTOR in PFC of male NMRI mice.

Lithium chloride clinically used to treat mental diseases but it has some side effects like cognitive impairment, memory deficit. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is able to change neural activity and gene transcription in the brain. The aim of the study is to provide a conceptual theoretical framework based on behavioral and molecular effects of tDCS on memory changes induced by lithium in male mice. we applied Anodal-tDCS and Cathodal-tDCS over the left PFC for 3 consecutive days tDCS for 20min with 2mA after injection of different doses of lithium/saline.Trained in fear condition and finally the day after that tested their memory persistency factors (freezing-latency) and other behavior such as grooming and rearing percentage time in the fear conditioning. P-mTOR/mTOR was analyzed using western blotting. The results obtained from the preliminary analysis of behavioral fear memory showed that lithium had destructive effect in higher doses and decreased freezing percentage time. However, both cathodal and anodal tDCS significantly improved memory and increased P-mTOR/mTOR level in the PFC. The results of this study indicate that cathodal and anodal tDCS upon the left prefrontal increased memory and reduced lithium side effects on memory consolidation and altered expression of plasticity-associated genes in the prefrontal cortex.

The BAFFling persistence of memory B cells.

Although BAFF/BLyS and its receptor, BAFFR, play critical roles in naive B cell survival, the pathways involved in the persistence of memory B cells are largely unknown. In this issue of JEM, two groups, Müller-Winkler et al. (https://doi.org/10.1084/jem.20191393) and Lau et al. (https://doi.org/10.1084/jem.20191167), take complementary approaches to identify an essential role for BAFFR in the survival of memory B cells.

Categorical Auditory Working Memory in Crows.

SummaryThe ability to group sensory data into behaviorally meaningful classes and to maintain these perceptual categories active in working memory is key to intelligent behavior. Here, we show that carrion crows, highly vocal and cognitively advanced corvid songbirds, possess categorical auditory working memory. The crows were trained in a delayed match-to-category task that required them to flexibly match remembered sounds based on the upward or downward shift of the sounds' frequency modulation. After training, the crows instantaneously classified novel sounds into the correct auditory categories. The crows showed sharp category boundaries as a function of the relative frequency interval of the modulation. In addition, the crows generalized frequency-modulated sounds within a category and correctly classified novel sounds kept in working memory irrespective of other acoustic features of the sound. This suggests that crows can form and actively memorize auditory perceptual categories in the service of cognitive control of their goal-directed behaviors.

Epinephrine May Contribute to the Persistence of Traumatic Memories in a Post-traumatic Stress Disorder Animal Model.

The importance of catecholamines in post-traumatic stress disorder (PTSD) still needs to be explored. We aimed to evaluate epinephrine’s (EPI) causal role and molecular mechanism for the persistence of PTSD traumatic memories. Wild-type (WT) and EPI-deficient mice (phenylethanolamine-N-methyltransferase-knockout mice, Pnmt-KO) were induced with PTSD and behavioral tests were performed. Some Pnmt-KO mice were administered with EPI or vehicle. Catecholamines were quantified by HPLC-ED. Nr4a1, Nr4a2, and Nr4a3 mRNA expression were evaluated by real-time PCR in hippocampus samples. It was observed an increase in EPI and freezing behavior, and a decrease in open arm entries in the elevated plus-maze test and time spent in the light in the light–dark test in WT mice in the PTSD-induction group compared to control. After induction of PTSD, Pnmt-KO mice showed a decrease in freezing, as well as an increase in open arm entries and transitions between compartments compared to WT. After PTSD induction, Pnmt-KO mice administered with EPI showed an increase in freezing compared with the vehicle. On day 0 of PTSD induction, it was observed an increase in mRNA expression of Nr4a2 and Nr4a3 genes in the hippocampus of WT mice compared to control, contrary to Pnmt-KO mice. In conclusion, our data suggest that EPI may be involved in the persistence of traumatic memories in PTSD, possibly through enhancement of the expression of Nr4a2 and Nr4a3 genes in the hippocampus. Peripheral administration of EPI restored contextual traumatic memories in Pnmt-KO mice, which suggests a causal role for EPI. The persistence of contextual traumatic memories may contribute to anxiety-like behavior and resistance of traumatic memory extinction in this PTSD mice model.

Intrusive memories: A mechanistic signature for emotional memory persistence

Memories of negative emotional events persist more over time relative to memories for neutral information. Such persistence has been attributed to heightened encoding and consolidation processes. However, reactivation of the encoded information may also lead to reduced memory decay through rehearsal or a reconsolidation processes. Here, we tested whether involuntary intrusive memories, spontaneously arising following a stressful event and reactivating its memory, function to prevent memory decay, enhancing its persistence. Participants watched a stressful film containing scenes of aversive material. Memory for the film contents was tested immediately post-film using a visual recognition test. In the following five days, participants recorded intrusive memories of the film using a digitized diary. After 5-days, memory for the film contents was retested. Results indicate that in the immediate aftermath of film watching, participant's memory scores were similarly high for scenes that were later experienced as intrusions and scenes that did not intrude, suggesting effective encoding for all scenes. However, persistence of memory for scenes that intruded was preserved relative to memory for scenes that did not intrude, pointing to a mechanism through which negative intrusive memories persist over time. Implications for memory modification interventions in trauma-related psychopathology are discussed.

Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between.

Maladaptive emotional memories contribute to the persistence of many mental health disorders, and therefore the prospect of disrupting these memories to produce long-term reductions in relapse is of great clinical appeal. Reducing the impact of maladaptive emotional memories on behaviour could be achieved by two retrieval-dependent manipulations that engage separate mnemonic processes: “reconsolidation disruption” and “extinction enhancement.” Extinction occurs during a prolonged re-exposure session in the absence of the expected emotional outcome and is widely accepted as reflecting the formation of a new, inhibitory memory that prevents behavioural expression of the original trace. Reconsolidation, by contrast, involves the destabilisation of the original memory, allowing for subsequent updating and restabilisation in specific brain regions, unless the re-stabilization process is prevented through specific pharmacological or behavioural interventions. Both destabilisation of the original memory and memory extinction require that re-exposure induces prediction error—a mismatch between what is expected and what actually occurs—but the parameters that allow reconsolidation and extinction to occur, and control the transition between them, have not been well-characterised. Here, we review what is known about the induction of memory destabilisation and extinction, and the transition period that separates these mnemonic processes, drawing on preclinical and clinical examples. A deeper understanding of the processes that determine the alternative routes to memory persistence or inhibition is critical for designing new and more reliable clinical treatments targeting maladaptive emotional memories.

Heplisav-B: A Hepatitis B Vaccine With a Novel Adjuvant.

To review the immunogenicity and safety of a hepatitis B vaccine containing the cytosine phosphoguanosine (CpG) 1018 adjuvant (HepB-CpG). Literature searches were performed using PubMed and Scopus with the search terms hepatitis B vaccine, HepB-CpG, CpG 1018, 1018-ISS, HBsAg-1018, HBV-ISS, and Heplisav. Other sources included the Centers for Disease Control, the Food and Drug Administration, the Advisory Committee on Immunization Practices (ACIP), and prescribing information. Search limits included randomized controlled trial in humans and published in English from January 2003 to August 2020. Studies using the final formulation and dosing schedule were reviewed. Studies demonstrated that 2 doses of HepB-CpG induced significantly higher seroprotective responses with a faster onset in adults, including those in hyporesponsive populations, compared with 3 doses of alum-adjuvanted Engerix-B. Although the safety profile was comparable to that of Engerix-B, one study observed higher rates of acute myocardial infarction, herpes zoster, and death with HepB-CpG. ACIP recommends use of HepB-CpG as an option to prevent hepatitis B virus infection in adults ≥18 years old. Higher immune responses after 2 doses make it a promising option, especially in those with risk factors for hyporesponsiveness or at risk for poor adherence to vaccine series completion. Additional data are needed regarding the vaccine's safety in the general population and the persistence of its antibody response. HepB-CpG has been shown to be as immunogenic as Engerix-B; however, long-term safety and persistence of immune memory has yet to be established.

Sustainable Shape-Memory Polyurethane from Abietic Acid: Superior Mechanical Properties and Shape Recovery with Tunable Transition Temperatures.

A new chemical architecture from abietic acid, consisting of a cycloaliphatic unsaturated terminal diisocyanate (AADI) structure, is synthesized and fully characterized. The AADI is then used to construct an amorphous and biocompatible shape-memory polyurethane (SMPU) network system with adjustable cross-linking densities over a wide range. The SMPU network exhibits good shape-memory properties with a shape fixing rate of greater than 98 % and a shape recovery rate of 95 %. In vitro hydrolytic biodegradation weight loss ratio of SMPUs reaches 71 % within eight weeks. The physical properties of these SMPUs are comparable to those reported for SMPUs obtained from commercially available petroleum-derived diisocyanates. This is the first time that multiple SMPU networks based on abietic acid have been reported. These environmentally-friendly SMPUs display a wide range of physicomechanical properties with promising hydrolytic degradability, showing good potential for practical application.

Quasideterministic dynamics, memory effects, and lack of self-averaging in the relaxation of quenched ferromagnets.

We discuss the interplay between the degree of dynamical stochasticity, memory persistence, and violation of the self-averaging property in the aging kinetics of quenched ferromagnets. We show that, in general, the longest possible memory effects, which correspond to the slowest possible temporal decay of the correlation function, are accompanied by the largest possible violation of self-averaging and a quasideterministic descent into the ergodic components. This phenomenon is observed in different systems, such as the Ising model with long-range interactions, including the mean-field, and the short-range random-field Ising model.

Persistence of Fear Memory Depends on a Delayed Elevation of BAF53b and FGF1 Expression in the Lateral Amygdala.

Endurance represents a highly adaptive function of fear memory and a major cause of maladaptive fear- and anxiety-related mental disorders. However, less is known about the mechanisms underlying the persistence of fear memory. The epigenetic gene regulation recently emerged as an important mechanism for memory persistence. In the previous study, we found that BAF53b, a neuron-specific subunit of BAF chromatin remodeling complex, is induced after auditory cued fear conditioning in the lateral amygdala (LA) and is crucial for recent fear memory formation. In this study using mice of both sexes, we report a delayed induction of BAF53b in the LA 48 h after auditory fear conditioning and its critical role for the persistence of established fear memory. To specifically block the delayed but not the early induced BAF53b function, we used a postlearning knock-down method based on RNAi. The transient knockdown of Baf53b using siRNA in the lateral amygdala 24 h after cued fear conditioning led to specific impairment of remote but not recent memory retrieval. RNA-sequencing analyses identified fibroblast growth factor 1 (FGF1) as a candidate downstream effector. Consistently, postlearning administration of FGF1 peptide rescued memory persistence in Baf53b knock-down mice. These results demonstrate the crucial role of BAF53b and FGF1 in persistent retention of fear memory, giving insights into how fear memory persistently stored through consolidation processes and suggest candidate target for treating mental disorders related to traumatic memory.SIGNIFICANCE STATEMENT It is still unclear how once consolidated memory persists over time. In this study, we report the delayed induction of nucleosome remodeling factor BAF53b in the lateral nucleus of amygdala after fear learning and its crucial role for persistence of established memory beyond 24 h after learning. Our data link the regulation of BAF53b and fibroblast growth factor 1 expression in the amygdala to fear memory persistence. Results from this study open a new direction to understand the time-dependent continuous consolidation processes potentially by a nucleosome-remodeling mechanism enabling long-lasting memory formation and give insights into how to treat mental disorders caused by enduring traumatic memory.

Abstract CT056: Durable complete responses to adoptive cell transfer using tumor infiltrating lymphocytes (TIL) in non-small cell lung cancer (NSCLC): A phase I trial

Abstract Study Objectives: A hallmark of tumor infiltrating lymphocytes (TIL) in melanoma is the potential for a complete response (CR) which can last for decades. This long-lived effect is attributed to persistence of memory T cells. However, clinical efficacy in metastatic non-small cell lung cancer (mNSCLC) has not previously been reported. We launched a phase I trial with the objective to evaluate the safety and efficacy in mNSCLC after evidence of progression on nivolumab. Methodology: Full eligibility criteria is described in trial registry (NCT03215810). Patients were required to have mNSCLC with at least 1 RECIST measurable lesion and also 1 lesion safely accessible for excisional biopsy, usually a supraclavicular lymph node or pleural nodule. This histologically confirmed metastasis was resected and TIL cultured. Autologously reactive cultures were pooled and cryopreserved. TIL was successfully expanded in 95% of patients, to a median dose of 103 billion CD3+ cells. Patients received nivolumab for 4 cycles with two serial CT scans. Patients with tumor enlargement or new lesions proceeded to lymphodepletion cyclophosphamide/fludarabine (Cy/Flu), TIL, and attenuated IL-2. After first CT scan, patients resumed nivolumab for up to 11 doses to augment TIL persistence. Results: Of 32 patients screened, 20 were eligible and enrolled. Median age 54 yrs (range 38 - 75), median PD-L1 proportion score 6%, median estimated TMB 5 mut/MB, 20% EGFR-mutant. The majority had bulky disease with mean sum of target lesion diameters of 7.0 cm. Of 20 enrolled, 13 had evidence of progression on nivolumab and received subsequent Cy/Flu/TIL/IL-2. Two more are progressing on nivolumab and set to receive TIL within next 2 months. Common non-hematologic adverse events (AEs) of the Cy/Flu/TIL/IL2 regimen included hypoalbuminemia (92%), hypophosphatemia (85%), nausea (77%), hyponatremia (69%), diarrhea (62%), the majority of these AEs resolving by Day +10 post-TIL. Initial tumor regression occurred in most patients at their first post-TIL CT scan, with the median best overall change in sum of target lesion diameters of -38% (range +20 to -100). Median time-on-trial post-TIL is 1.4 years. Two patients have achieved durable CRs which are still ongoing almost 1 year post-TIL. One is a never-smoker with EGFREx19 mutation and PD-L1 1%. Three additional patients were able to maintain a clinical remission by local ablative therapy of an isolated new lesion performed 6 to 17 months post-TIL. Persistence of the infused TCR-Vβ clonotypes at post-infusion timepoints was associated with clinical benefit. Neoantigen-specific T cells were detected in the TIL and post-TIL peripheral blood. Conclusions: TIL has manageable toxicity and capacity to achieve durable remission in mNSCLC after nivolumab treatment. TIL may be a promising option for fit mNSCLC patients. Citation Format: Ben Creelan, Chao Wang, Jamie Teer, Eric Toloza, John Mullinax, Jiqiang Yao, John Koomen, Sungjune Kim, Alberto Chiappori, James Saller, Leighann Montoya, Ana Marie Landin, Tawee Tanvetyanon, Bin Fang, Zachary Thompson, Xiaoping Yu, Andreas Saltos, Dung-Tsa Chen, Jose Conejo-Garcia, Eric Haura, Scott Antonia. Durable complete responses to adoptive cell transfer using tumor infiltrating lymphocytes (TIL) in non-small cell lung cancer (NSCLC): A phase I trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT056.

Multiple developmental pathways lead to the generation of CD4 T-cell memory

Long-term immunological memory mediated by CD4 T cells provides a rapid protection against previously encountered pathogens or antigens. However, it is still controversial how memory CD4 T cells are generated and maintained. Unclear definitions of T-cell memory may be partially responsible for this controversy. It is becoming clear that diverse pathways are responsible for the differentiation and long-term persistence of memory T cells. We herein discuss the diversity of memory cell generation, describing a novel population of resting memory CD4 T cells and their precursors.

Memory reconsolidation as a tool to endure encoding deficits in elderly.

Normal aging involves changes in the ability to acquire, consolidate and recall new information. It has been recently proposed that the reconsolidation process is also affected in older adults. Reconsolidation is triggered after reminder presentation, allowing memories to be modified: they can be impaired, strengthened or changed in their content. In young adults it was previously shown that the presentation of repetitive reminders induces memory strengthening one day after reactivation and the presentation of at least one reminder increases memory persistence several days after reactivation. However, until now this process has remained elusive in older adults. We hypothesize that older adults need a stronger reminder to induce memory strengthening through the reconsolidation process than young adults. To test this, we perform a three-day experiment. On day 1, participants learned 15 sound-word associations, on day 2 they received no reminders (NR group), one reminder (R group) or two rounds of reactivations (Rx2 group). Finally, they were tested on day 7. We found that, contrary to our hypothesis, older adults show a memory improvement triggered by repeated labilization/reconsolidation processes to an equal extent than young adults. These results open new perspectives into the use of reconsolidation to improve daily acquired information and the development of therapeutic home used tools to produce memory enhancement in healthy older adults or those with cognitive decline.

The role of prelimbic and anterior cingulate cortices in fear memory reconsolidation and persistence depends on the memory age.

Reconsolidation is a time-limited process under which reactivated memory content can be modified. Works focused on studying reconsolidation mainly restrict intervention to the moments immediately after reactivation and to recently acquired memories. However, the brain areas activated during memory retrieval depend on when it was acquired, and it is relatively unknown how different brain sites contribute to reconsolidation and persistence of reactivated recent and remote fear memories. Here, we sought to investigate the participation of prelimbic (PL) and anterior cingulate cortices (ACC) in recent (1 d old) and remote (21 d old) fear memory reconsolidation and persistence. Male Wistar rats were submitted to the contextual fear conditioning protocol. Tamoxifen (TMX), an estrogen receptor modulator known to inhibit protein kinase C activity was used to interfere with these processes. When infused into the PL cortex, but not into the ACC, TMX administration immediately or 6 h after recent fear memory reactivation impaired memory reconsolidation and persistence, respectively. TMX administered immediately after remote memory reactivation impaired memory reconsolidation when infused into the PL cortex and ACC. However, remote memory persistence was only affected when TMX was infused 6 h after memory reactivation into the ACC and no effect was observed when TMX was infused 6 h after memory reactivation into PL cortex. Together, the findings provide further evidence on the participation of PL cortex and ACC in reconsolidation of recent and remote fear memories and suggest that the persistence of a reactivated fear memory becomes independent on the PL cortex with memory age and dependent on the ACC.