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- Artículo de Publicación PeriódicaAMPA receptors: A key piece in the puzzle of memory retrieval.(2021) Pereyra, Magdalena; Medina, Jorge Horacio"Retrieval constitutes a highly regulated and dynamic phase in memory processing. Its rapid temporal scales require a coordinated molecular chain of events at the synaptic level that support transient memory trace reactivation. AMPA receptors (AMPAR) drive the majority of excitatory transmission in the brain and its dynamic features match the singular fast timescales of memory retrieval. Here we provide a review on AMPAR contribution to memory retrieval regarding its dynamic movements along the synaptic compartments, its changes in receptor number and subunit composition that take place in activity dependent processes associated with retrieval. We highlight on the differential regulations exerted by AMPAR subunits in plasticity processes and its impact on memory recall"
- Artículo de Publicación PeriódicaBehavioral tagging underlies memory reconsolidation(2020-07) Rabinovich Orlandi, Iván; Fullio, Camila L.; Schroeder, Matías Nicolás; Giurfa, Martin; Ballarini, Fabricio; Moncada, Diego"Memory reconsolidation occurs when a retrieving event destabilizes transiently a consolidated memory, triggering thereby a new process of restabilization that ensures memory persistence. Although this phenomenon has received wide attention, the effect of new information cooccurring with the reconsolidation process has been less explored. Here we demonstrate that a memory retrieving event sets a neural tag, which enables the reconsolidation of memory after binding proteins provided by the original or a different contiguous experience. We characterized the specific temporal window during which this association is effective and identified the protein kinase A (PKA) and the extracellular signalregulated kinase 1 and 2 (ERK 1/2) pathways as the mechanisms related to the setting of the reconsolidation tag and the synthesis of proteins. Our results show, therefore, that memory reconsolidation is mediated by a “behavioral tagging” process, which is common to different memory forms. They represent a significant advance in understanding the fate of memories reconsolidated while being adjacent to other events, and provide a tool for designing noninvasive strategies to attenuate (pathological/traumatic) or improve (education-related) memories. "
- Artículo de Publicación PeriódicaClassification based on dynamic mode decomposition applied to brain recognition of context(2021-09) Martínez, Sebastián; Silva, Azul; García Violini, Demián; Piriz, Joaquin; Belluscio, Mariano; Sánchez-Peña, Ricardo"Local Field Potentials (LFPs) are easy to access electrical signals of the brain that represent the summation in the extracellular space, of currents originated within the neurons. As such, LFPs could contain infor mation about ongoing computations in neuronal circuits and could potentially be used to design brain machine interface algorithms. However how brain computations could be decoded from LFPs is not clear. Within this context, a methodology for signal classification is proposed in this study, particularly based on the Dynamic Mode Decomposition method, in conjunction with binary clustering routines based on supervised learning. Note that, although the classification methodology is presented here in the context of a biological problem, it can be applied to a broad range of applications. Then, as a case-study, the proposed method is validated with the classification of LFP-based brain cognitive states. All the analysis, signals, and results shown in this study consider real data measured in the hippocampus, in rats perform ing exploration tasks. Consequently, it is shown that, using the measured LFP, the method infers which context was the animal exploring. Thus, evidence on the spatial codification in LFP signals is consequently provided, which still is an open question in neuroscience."
- Artículo de Publicación PeriódicaDifferential neurophysiological correlates of retrieval of consolidated and reconsolidated memories in humans: an ERP and pupillometry study(2020-10) Campos-Arteaga, G.; Forcato, Cecilia; Wainstein, G.; Lagos, R.; Palacios-García, I.; Artigas, C.; Morales, R.; Pedreira, María Eugenia; Rodríguez, E."Consolidated memories can return to a labile state if they are reactivated by unpredictable reminders. To persist, active memories must be re-stabilized through a process known as reconsolidation. Although there is consistent behavioral evidence about this process in humans, the retrieval process of reconsolidated memories remains poorly understood. In this context, one fundamental question is whether the same or different neurophysiological mechanisms are involved in retrieval of consolidated and reconsolidated memories. Because it has been demonstrated that the exposure to the reconsolidation process may restructure and strengthen memories, we hypothesized distinct neurophysiological patterns during retrieval of reconsolidated memories. In addition, we hypothesized that interfering with the reconsolidation process using a new learning can prevent these neurophysiological changes. To test it, consolidated, reconsolidated and declarative memories whose reconsolidation process was interfered (i.e., picture-word pairs) were evaluated in humans in an old/new associative recall task while the brain activity and the pupillary response were recorded using electroencephalography and eyetracking. Our results showed that retrieval of reconsolidated memories elicits specific patterns of brain activation, characterized by an earlier peak latency and a smaller magnitude of the left parietal ERP old/new effect compared to memories that were only consolidated or whose reconsolidation process was interfered by a new learning. Moreover, our results demonstrated that only retrieval of reconsolidated memories is associated with a late reversed mid-frontal effect in a 600–690 time window. Complementarily, memories that were reactivated showed an earlier peak latency of the pupil old/new effect compared to non-reactivated memories. These findings support the idea that reconsolidation has an important impact in how memories are retrieved in the future, showing that retrieval of reconsolidated memories is partially supported by specific brain mechanisms."
- Artículo de Publicación PeriódicaDopamine D1/D5 receptors in the restrosplenial cortex are necessary to consolidate object recognition memory(2022-07-22) de Landeta, Ana Belén; Medina, Jorge Horacio; Katche, Cynthia"The retrosplenial cortex (RSC) has been widely related to spatial and contextual memory. However, we recently demonstrated that the anterior part of the RSC (aRSC) is required for object recognition (OR) memory consolidation. In this study, we aimed to analyze the requirement of dopaminergic inputs into the aRSC for OR memory consolidation in male rats. We observed amnesia at 24-h long-term memory when we infused SCH23390, a D1/D5 dopamine receptors antagonist, into aRSC immediately after OR training session. However, the same infusion had no effect on OR short-term memory. Then, we analyzed whether the ventral tegmental area (VTA) is necessary for OR consolidation. VTA inactivation by intra-VTA administration of muscimol, a GABAA agonist, immediately after an OR training session induced amnesia when animals were tested at 24 h. Moreover, we observed that this VTA inactivation-induced amnesia was reversed by the simultaneous intra-aRSC delivery of SKF38393, a D1/D5 receptor agonist. Altogether, our results suggest that VTA dopaminergic inputs to aRSC play an important modulatory role in OR memory consolidation."
- Artículo de Publicación PeriódicaDopamine neurotransmission in the VTA regulates aversive memory formation and persistence(2022-09-01) Castillo Díaz, Fernando; Dalto, Juliana F.; Pereyra, Magdalena; Medina, Jorge Horacio"Dopamine (DA) neurons in the ventral tegmental area (VTA) innervating several limbic and neocortical regions of the mammalian brain have long been implicated in motivation, rewarding and aversive behaviors, and memory processing. Recently, we demonstrated that somatodendritic release of DA in the VTA regulates the formation and maintenance of appetitive long-term memories (LTM). However, less is known about the impact of DA neurotransmission in the VTA on aversive LTM. Here, we describe the modulation of negative-valence memories by D1/D5-type DA (D1R)-receptor-mediated neurotransmission in the VTA. As aversive stimuli elicit both active and passive behavioral responses, we used two single-trial aversive training protocols: inhibitory avoidance task and conditioned place aversion. We bilaterally microinfused SCH23390, an antagonist of D1R, into the VTA immediately after training and found that DA neurotransmission in the VTA modulates LTM consolidation and persistence of aversive experiences. Together with previous findings demonstrating that D1R mediated DA neurotransmission in the medial prefrontal cortex and hippocampus is involved in the formation and persistence of LTM for aversive events, our present results indicate that memory processing of environmental stimuli with negative-valence depends on the integration of information mediated by D1R activation in both the VTA region and in selected downstream target areas."
- Artículo de Publicación PeriódicaDynamical models in neuroscience from a closed-loop control perspective(2022-01-28) Martínez, Sebastián; García Violini, Demián; Belluscio, Mariano; Piriz, Joaquin; Sánchez-Peña, Ricardo"Modifying neural activity is a substantial goal in neuroscience that facilitates the understanding of brain functions and the development of medical therapies. Neurobiological models play an essential role, contributing to the understanding of the underlying brain dynamics. In this context, control systems represent a fundamental tool to provide a correct articulation between model stimulus (system inputs) and outcomes (system outputs). However, throughout the literature there is a lack of discussions on neurobiological models, from the formal control perspective. In general, existing control proposals applied to this family of systems, are developed empirically, without theoretical and rigorous framework. Thus, the existing control solutions, present clear and significant limitations. The focus of this work is to survey dynamical neurobiological models that could serve for closed-loop control schemes or for simulation analysis. Consequently, this paper provides a comprehensive guide to discuss and analyze control oriented neurobiological models. It also provides a potential framework to adequately tackle control problems that could modify the behavior of single neurons or networks. Thus, this study constitutes a key element in the upcoming discussions and studies regarding control methodologies applied to neurobiological systems, to extend the present research and understanding horizon for this field."
- Artículo de Publicación PeriódicaEPOC Emotiv EEG Basics(2022-10) Ramele, Rodrigo; Villar, Ana Julia; Santos, Juan MiguelThis document provides some basic guidance to start working with the EPOC Emotiv neuroheadset device and describes how to use it to perform basic Brain-Computer Interface (BCI) research. A brief tutorial on how to set up the device, from its electrophysiological point of view, as well as a description and practical code to perform some basic analysis, is explained. A basic experiment is introduced to detect one of the oldest and, indeed, quite still valuable electrophysiological correlate, visual occipital alpha waves, or Berger Rhythm. An additional experiment is expounded where the power spectrum of alpha waves is reduced when a subject is affected by background cognitive disturbances. This document also briefs about the extraction of information by using the EPOC Emotiv library and also with python Emokit package. This report presents a basic guide on how to use EEGLAB + MATLAB, as well as python stack to perform the neurophysiological analysis. Finally, a basic analysis on different feature extraction and classification methods is provided.
- Artículo de Publicación PeriódicaFunctional connectivity of anterior retrosplenial cortex in object recognition memory(2021) de Landeta, Ana Belén; Pereyra, Magdalena; Miranda, Magdalena; Bekinschtein, Pedro; Medina, Jorge Horacio; Katche, Cynthia"Recognition memory can rely on three components: “what”, “where” and “when”. Recently we demonstrated that the anterior retrosplenial cortex (aRSC), like the perirhinal cortex (PRH) and unlike the hippocampus (HP), is required for consolidation of the “what” component. Here, we aimed at studying which brain structures interact with the aRSC to process object recognition (OR) memory in rats. We studied the interaction of six brain structures that are connected to the aRSC during OR memory processing: PRH, medial prefrontal cortex (mPFC), anteromedial thalamic nuclei (AM), medial entorhinal cortex (MEC), anterior cingulate cortex (ACC) and the dorsal HP (dHP). We previously described the role of the PRH and dHP, so we first studied the participation of the mPFC, AM, MEC and ACC in OR memory consolidation by bilateral microinfusions of the GABAA receptor agonist muscimol. We observed an impairment in OR long-term memory (LTM) when inactivating the mPFC, the AM and the MEC, but not the ACC. Then, we studied the functional connections by unilateral inactivation of the aRSC and each one of the six structures in the same (ipsilateral) or the opposite (contralateral) hemisphere. Our results showed an amnesic LTM effect in rats with ipsilateral inactivations of aRSC-PRH, aRSC-mPFC, aRSC-AM, or aRSC-MEC. On the other hand, we observed memory impairment when aRSC-ACC were inactivated in opposite hemispheres, and no effect when the aRSC-dHP connection was inactivated. Thus, our ipsilateral inactivation findings reveal that the aRSC and, at least one brain region required in OR LTM processing are essential to consolidate OR memory. In conclusion, our results show that several cortico-cortical and cortico thalamic pathways are important for OR memory consolidation."
- Artículo de Publicación PeriódicaIdentification performance during quarantine by COVID-19 pandemic: Influence of emotional variables and sleep quality(2021) Urreta Benítez, Facundo A.; León, Candela S.; Bonilla, Matías; Flores-Kanter, Pablo Ezequiel; Forcato, Cecilia"The COVID-19 pandemic has caused major disruptions in people’s lives around the globe. Sleep habits and emotional balance have been disturbed in a way that could be comparable to the havoc caused by a deep personal crisis or a traumatic experience. This unfortunate situation provides a unique context in which to study the impact of these imbalances on cognitive processes. In particular, the field of eyewitness science could benefit from these conditions, since they are also often present in crime victims, but can only be generated in the laboratory up to a certain ethical and practical limit. For several decades, eyewitness studies have tried to discover what variables affect people’s ability to properly recognize faces. However, the disparity of experimental designs and the limitations of laboratory work could be contributing to the lack of consensus around several factors, such as sleep, anxiety, and depression. Therefore, the possibility of observing the influence of these agents in natural contexts could shed light on this discussion. Here, we perform simple and repeated lineups with witnesses of mock-crime, considering the conditions related to the COVID-19 pandemic, which to some extent allow emulating the deterioration in general well-being that often afflicts crime victims. For this, 72 participants completed symptomatology scales, and watched a video portraying a staged violent episode. Subsequently, they gave testimony and participated in two lineups, in which we manipulated the presence/absence of the perpetrator, to recreate critical scenarios for the appearance of false recognitions. We found an increase in recognition errors in those individuals who did not have access to the perpetrator during the Initial lineup. Additionally, the conditions of the pandemic appear to have adversely affected the ability to witness and accurately perform lineups. These results reaffirm the need to move toward the standardization of research practices and methods for assessing testimonial evidence, especially in relation to the results of the lineups. Considering the degree of fallibility of these processes can lead to a reduction of wrongful convictions."
- Artículo de Publicación PeriódicaImpairment of aversive episodic memories during Covid-19 pandemic: The impact of emotional context on memory processes(2022-06) León, Candela S.; Bonilla, Matías; Urreta Benítez, Facundo A.; Brusco, Luis Ignacio; Wang, Jingyi; Forcato, Cecilia"The threatening context of the COVID-19 pandemic provided a unique setting to study the effects of negative psychological symptoms on memory processes. Episodic memory is an essential function of the human being related to the ability to store and remember experiences and anticipate possible events in the future. Studying this function in this context is crucial to understand what effects the pandemic will have on the formation of episodic memories. To study this, the formation of episodic memories was evaluated by free recall, recognition, and episode order tasks for an aversive and neutral content. The results indicated that aversive episodic memory is impaired both in the free recall task and in the recognition task. Even the beneficial effect that emotional memory usually has for the episodic order was undermined as there were no differences between the neutral and aversive condition. The present work adds to the evidence that indicates that the level of activation does not modify memory processes in a linear way, which also depends on the type of recall and the characteristics of the content to be encoded."
- Artículo de Publicación PeriódicaInternal Structure of Beck Hopelessness Scale: an analysis of method effects using the CT-C(M–1) model(2021) Flores-Kanter, Pablo Ezequiel; Toro, Ronald; Alvarado, Jesús M."He construct validity in relation to the dimensionality or factor structure of the Beck Hopelessness Scale (BHS) has long been debated in psychometrics. Irrelevant variance due to item wording (method effects) can distort the factor structure, and recent studies have examined the method factor’s role in the factor structure of the BHS. However, the models used to control the method effects have severe limitations, and new models are needed. One such model is the correlated traitcorrelated method minus one (CT-C(M-1), which is a powerful approach that gives the trait factor an unambiguous meaning and prevents the anomalous results associated with fully symmetrical bifactor modeling. The present work compares the fit and factor structure of the CT-C(M-1) model to bifactor models proposed in previous literature and evaluates the convergent validity of the CT-C(M-1) model and its discriminatory capacity by taking suicidal ideation as the criterion variable. This study used a large and heterogeneous open mode online sample of Argentinian people (N = 2,164). The results indicated that the CT-C(M-1) model with positive words as referenced items achieves the most adequate factor structure. The factorial scores derived from this model demonstrate good predictive and discriminating capabilities."
- Artículo de Publicación PeriódicaInventario de Ideación Suicida Positiva y Negativa (PANSI): propiedades psicométricas en universitarios peruanos(2021) Rodas-Vera, Nikolai Martin; Toro, Ronald; Flores-Kanter, Pablo Ezequiel"Es necesario contar con instrumentos que evalúen la ideación suicida, dado que es uno de los primeros factores que conllevan al suicidio. La presente investigación realizó un proceso de adaptación del Inventario de Ideación Suicida Positiva y Negativa (PANSI) para que pueda ser empleado en universitarios peruanos. Se estudiaron dos muestras, una antes y otra durante la pandemia por COVID-19. A nivel metodológico, se siguió un procedimiento racional con jueces expertos y con sujetos de la población para conseguir la equivalencia cultural y conceptual del instrumento; mientras que, en el nivel estadístico, se probaron tres modelos teóricos, unidimensional, ortogonal y oblicuo. El modelo de dos factores correlacionados reveló mejores índices de ajustes para ambas muestras, con niveles óptimos de confiabilidad. Se concluye en una nueva versión del PANSI y se discuten sus bases teóricas para mejorar las inferencias a partir de este instrumento."
- Artículo de Publicación PeriódicaLearning new words: memory reactivation as a mechanism for strengthening and updating a novel word´s meaning(2020-12) Laurino, Julieta; Forcato, Cecilia; Coaker, Nicole; Pedreira, María Eugenia; Kaczer, Laura"In the present study we explored the post-learning changes in a novel word’s definition using a cue-induced memory reactivation. Native speakers of Spanish (N=373) learned low-frequency words with their corresponding definitions. The following day, reactivated groups were exposed to a reminder and provided a subjective assessment of reactivation for each word, while control groups did not receive a reactivation. Study A demonstrated that memory reactivation enhances both explicit recall and semantic integration of new meanings. Study B investigated the effect of memory reactivation in the modification of the new meanings, through three different experiments. Results show an improvement of the updated definitions according to each word´s reactivation strength. In addition, congruence with previous knowledge was found to be a boundary condition, while consolidation time had a positive modulatory effect. Our findings call attention to reactivation as a factor allowing for malleability as well as persistence of long-term memories for words."
- Artículo de Publicación PeriódicaMedial prefrontal cortical control of reward- and aversion-based behavioral output: bottom-up modulation(2021-03-04) Pastor, Verónica; Medina, Jorge Horacio"How does the brain guide our actions? This is a complex issue, where the medial prefrontal cortex (mPFC) plays a crucial role. The mPFC is essential for cognitive flexibility and decision making. These functions are related to reward- and aversionbased learning, which ultimately drive behavior. Though, cortical projections and modulatory systems that may regulate those processes in the mPFC are less understood. How does the mPFC regulate approach-avoidance behavior in the case of conflicting aversive and appetitive stimuli? This is likely dependent on the bottomup neuromodulation of the mPFC projection neurons. In this review, we integrate behavioral-, pharmacological-, and viral-based circuit manipulation data showing the involvement of mPFC dopaminergic, noradrenergic, cholinergic, and serotoninergic inputs in reward and aversion processing. Given that an incorrect balance of reward and aversion value could be a key problem in mental diseases such as substance use disorders, we discuss outstanding questions for future research on the role of mPFC modulation in reward and aversion."
- Artículo de Publicación PeriódicaMemory reconsolidation as a tool to endure encoding deficits in elderly(2020-08) Tassone, Leonela M.; Urreta Benítez, Facundo A.; Rochon, Delfina; Martínez, Paula B.; Bonilla, Matías; León, Candela S.; Muchnik, Carolina; Solis, Patricia; Medel, Nancy; Kochen, Silvia; Brusco, Luis Ignacio; Moyano, Malen D.; Forcato, Cecilia"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."
- Artículo de Publicación PeriódicaModificación de memorias maladaptativas durante el sueño y la vigilia: una visión interdisciplinaria(2020-11-20) Bonilla, Matías; Jorge, Camila Isabel; Moyano, Malen D.; Forcato, Cecilia"Las memorias consolidadas pueden atravesar por un período de labilidad frente a la presentación de recordatorios (claves ligadas al aprendizaje inicial), seguido de un proceso de re-estabilización conocido como reconsolidación. Por otro lado, el sueño tiene un rol activo en la formación y modificación de memorias, así como en la reducción del tono emocional de las experiencias. Durante el mismo, las nuevas memorias se reactivan, refuerzan e integran a las redes mnésicas preexistentes. Dentro del contexto terapéutico, se pueden evocar memorias antiguas según la necesidad del sujeto, lo que podría estar desencadenando constantes labilizaciones/reestabilizaciones, quizás sin ser conscientes de ello. En la presente revisión bibliográfica discutimos los avances neurocientíficos relacionados a la reactivación y modificación de memorias durante la vigilia y el sueño, así como los últimos desarrollos en terapias psicoterapéuticas para trastornos de ansiedad, con el objetivo de pensar una práctica más interdisciplinaria."
- Artículo de Publicación PeriódicaNon-linear susceptibility to interferences in declarative memory formation(2022-06-29) Moyano, Malen D.; Carbonari, Giulia; Bonilla, Matías; Pedreira, María Eugenia; Brusco, Luis Ignacio; Kaczer, Laura; Forcato, Cecilia"After encoding, memories go through a labile state followed by a stabilization process known as consolidation. Once consolidated they can enter a new labile state after the presentation of a reminder of the original memory, followed by a period of re-stabilization (reconsolidation). During these periods of lability the memory traces can be modified. Currently, some studies show a rapid stabilization after 30 min, while others show that stabilization occurs after longer periods (e.g. > 6 h). Here we investigate the effect of an interference treatment on declarative memory consolidation, comparing distinct time intervals after acquisition. On day 1, participants learned a list of non- syllable pairs (List 1). 5 min, 30 min, 3 h or 8 h later, they received an interference list (List 2) that acted as an amnesic agent. On day 2 (48 h after training) participants had to recall List 1 first, followed by List 2. We found that the List 1 memory was susceptible to interference when List 2 was administered 5 min or 3 h after learning but not when it was administered 30 min or 8 h after. We propose the possibility that this rapid memory protection could be induced by a fast and transient neocortical integration. Our results open a discussion about the contribution of molecular and systemic aspects to memory consolidation."
- Artículo de Publicación PeriódicaOdor cueing during sleep improves consolidation of a history lesson in a school setting(2022-03-22) Vidal, Vanesa; Barbuzza, Alejo R.; Tassone, Leonela M.; Brusco, Luis Ignacio; Ballarini, Fabricio; Forcato, Cecilia"Sleep is a key factor in memory consolidation. During sleep, information is reactivated, transferred, and redistributed to neocortical areas, thus favoring memory consolidation and integration. Although these reactivations occur spontaneously, they can also be induced using external cues, such as sound or odor cues, linked to the acquired information. Hence, targeted memory reactivation during sleep represents an advantageous tool for improving memory consolidation in real-life settings. In this study, our goal was to improve the consolidation of complex information such as that of a history lesson, using a school study session in the presence of an odor, and a reactivation round while sleeping at home on the same night of the acquisition, without using additional study sessions. We found that complex information can be associated with an odor in the classroom and that one session of reactivation during the frst night of sleep in the students’ houses improves its consolidation. These results bring new evidence for the implementation of reactivation during sleep in real-life settings."
- Artículo de Publicación PeriódicaPersistence of spatial memory induced by spaced training involves a behavioral-tagging process(2022-08-10) Correa, Julieta; Tintorelli, Ramiro; Budriesi, Pablo; Viola, Haydeé"Spaced training, which involves long inter-trial intervals, has positive effects on memories. One of the main attributes of long-term memories (LTM) is persistence. Here, to identify the process that promotes LTM persistence by spaced learning, we used the spatial object recognition (SOR) task in rats. The protocol consisted of a first strong training session that induced LTM formation (tested 1 day after training), but not LTM persistence (tested 7 or 14 days after training); and a second weak training session that promoted memory persistence when applied 1 day, but not 7 days, after the first training. We propose that the promotion of memory persistence is based on the Behavioral Tagging (BT) mechanism operating when the memory trace is retrieved. BT involves the setting of a tag induced by learning which gives rise to input selectivity, and the use of plasticity-related proteins (PRPs) to establish the mnemonic trace. We postulate that retraining will mainly retag the sites initially activated by the original learning, where the PRPs needed for memory expression and/or induced by retrieval would be used to maintain a persistent mnemonic trace. Our results suggest that the mechanism of memory expression, but not those of memory reinforcement or reconsolidation, is necessary to promote memory persistence after retraining. The molecular mechanisms involve ERKs1/2 activity to set the SOR learning tag, and the availability of GluA2-containing AMPA receptor. In conclusion, both the synthesis of PRPs and the setting of learning tags are key processes triggered by retraining that allow SOR memory persistence."