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Models of episodic memory are successfully established using spontaneous object recognition tasks in rodents. In this review, we present behavioral techniques devised to investigate this type of memory, emphasizing methods based on associations of places and temporal order of items explored by rats and mice. We also provide a review on the areas and circuitry of the medial temporal lobe underlying episodic-like memory, considering that a large number of neurobiology data derived from these protocols. Although spontaneous recognition tasks are commonplace in this field, there is need for careful evaluation of factors affecting animal performance. Such as the ongoing development of tools for investigating the neural basis of memory, efforts should be put in the refinement of experimental designs, in order to provide reliable behavioral evidence of this complex mnemonic system.

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BACKGROUND: The performance of a task depends on ongoing brain activity, which can be influenced by attention, excitement, or motivation. Scientific studies have confirmed that mindfulness leads to better performance, health, and well-being. However, these cognitive efficiency modulating factors are nonspecific, can be difficult to control, and are not suitable to specifically facilitate neural processing. OBJECTIVE: The aim of this study is to evaluate the effects of transcranial direct current stimulation associated with neurofeedback on declarative memory and cerebral blood flow in university students. METHODS: In this study, we will use transcranial direct current stimulation, a low-cost physical resource that is easy to apply, has few adverse effects, and is associated with a neurofeedback resource. This, in turn, has been shown to be a training program capable of improving working memory function. RESULTS: Participants will be recruited between July 2022 and December 2022. This study is expected to conclude in July 2023. CONCLUSIONS: This study will provide preliminary results on the benefits of using the direct current neurostimulation and neurofeedback tools on the participants being analyzed. TRIAL REGISTRATION: Brazilian Clinical Trials Registry RBR-7zs8b5; https://ensaiosclinicos.gov.br/rg/RBR-7zs8b5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/36294.

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Stress alters memory. Understanding how and when acute stress improves or impairs memory is a challenge. Stressors can affect memory depending on a combination of factors. Typically, mild stressors and stress hormones might promote consolidation of memory processing and impair memory retrieval. However, studies have shown that during reconsolidation, stressors may either enhance or impair recalled memory. We propose that a function of reconsolidation is to induce changes in the behavioral expression of memory. Here, we adapted the Rey Auditory Verbal Learning Test (RAVLT) to evaluate the effect of cold pressor stress (CPS) during the reconsolidation of this declarative memory. A decay in memory performance attributable to forgetting was found at the time of memory reactivation 5 d after training (day 6). Contrary to our initial predictions, the administration of CPS after memory reactivation impaired long-term memory expression (day 7), an effect dependent on the presence of a mismatch during Reactivation Session. No differences in recognition tests were found. To assess putative sources of the negative memory modulation effects induced during reconsolidation, current emotional state was evaluated immediately after Testing Session (day 7). An increase in arousal was revealed only when CPS was administered concurrently with memory reactivation-labilization. The possibility of integration during reconsolidation of independent associations of these emotive components in the trace is a critical factor in modulating neutral memories during reconsolidation by stressors.

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Este artigo objetiva oferecer uma ampla revisão do framework da Teoria Declarativa/Procedural (DPT), de Michael Ullman, a partir de artigos publicados entre 1998, quando a DPT foi proposta, até 2016. A DPT sustenta que a aprendizagem da linguagem depende de dois sistemas de memória: o léxico é aprendido por memória declarativa, e as regras gramaticais, por memória procedural. Com esta revisão, os resultados obtidos são: (a) estudos com pacientes com distúrbios, utilizando neuroimagens, verificaram as áreas encefálicas ativadas durante a realização de atividades ligadas à linguagem e à memória; (b) identificação de que as memórias declarativa e procedural não são específicas da linguagem, pois atuam em habilidades motoras e recordações de fatos e eventos; (c) com o avanço das pesquisas, a DTP tornou-se mais flexível, admitindo que os sistemas de memória, mesmo independentes, interagem de várias formas; e (d) fatores como idade, frequência de exposição ao input linguístico, disfunções e hormônios impactam no uso dos dois sistemas.

This paper aims at providing a wide review of the Michael Ullman's Declarative/Procedural Theory framework from papers published between 1998 (when DPT was proposed) and 2016. The DPTclaims that the language learning depends upon two distinct memory systems: lexicon is learned by declarative memory, whereas grammar rules use procedural memory. From this review, the results are: (a) studies with patients with disorders, using neuroimaging, revealed regions of the encephalon that were activated during the performance of activities involving language and memory; (b) identification that the declarative and procedural memories are not domain-specific, since they act on motor abilities and retrieval of facts and events; c) with the improvement of the researches, Ullman's theory became more flexible, admitting that even though the memory systems are independent, they interact many times; and variables such as age, frequency, disorders and hormonal issues impact on the use of both memory systems.

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Esta investigación tuvo como objetivo determinar la influencia de las emociones en los procesos de memoria declarativa en personas con enfermedad de Alzheimer. Para esto, se planteó un estudio con diseño comparativo-correlacional y modelo no probabilístico. Participaron 160 adultos mayores, 80 con diagnóstico de enfermedad de Alzheimer y 80 con envejecimiento normal, homólogos en edad, género y nivel escolar. Se encontró que, de forma general, las emociones negativas favorecen la codificación, almacenamiento y evocación de la información en personas con Alzheimer, más que las positivas, y la mayor influencia se haya en contenidos de información asociados a emociones como miedo y tristeza. Asimismo, el brindar claves semánticas posibilita una mayor cantidad de información a ser evocada. La memoria en el envejecimiento normal y patológico se beneficia de los vínculos establecidos entre la información y las emociones contextuales al momento de registrarla y almacenarla, por lo que, siendo la memoria uno de los principales deterioros en la enfermedad de Alzheimer, este vínculo es clave en el abordaje de la patología y los programas de intervención clínica.

The objective of this research was to determine the influence of emotions on declarative memory processes in people with Alzheimer's disease. A study with a comparative-correlational design and a non-probabilistic model was proposed. 160 elderly people participated, 80 with a diagnosis of Alzheimer's disease and 80 with normal aging, homologous in age, gender and school level. It was found that in general negative emotions favor the coding storage and evocation of information in people with Alzheimer's disease, rather than positive ones, and the greatest influence is on information content associated with emotions such as fear and sadness. Likewise, providing semantic keys allows a greater amount of information to be evoked. Memory in normal and pathological aging benefits from the links established between information and contextual emotions at the time of recording and storing it since memory is one of the main impairments in Alzheimer's disease, this link is key in the approach of pathology and clinical intervention programs.

O objetivo desta pesquisa foi determinar a influência das emoções nos processos de memória declarativa em pessoas com doença de Alzheimer. Para isso, foi proposto um estudo com modelo comparativo-correlacional e não probabilístico. Participaram 160 idosos, sendo 80 com diagnóstico de doença de Alzheimer e 80 com envelhecimento normal, homólogos em idade, sexo e nível escolar. Achou-se que, em geral, as emoções negativas favorecem a codificação, armazenamento e evocação de informações em pessoas com doença de Alzheimer, ao invés das positivas, e a maior influência está no conteúdo de informação associado a emoções como medo e tristeza. Da mesma forma, fornecer chaves-semânticas permite que uma quantidade maior de informações seja evocada. A memória no envelhecimento normal e patológico se beneficia das ligações estabelecidas entre a informação e as emoções contextuais no momento de registrála e de armazená-la, de modo que, como a memória é um dos principais prejuízos na doença de Alzheimer, essa ligação é fundamental na abordagem da patologia e dos programas de intervenção clínica.

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RATIONALE: Cocaine base paste (CBP) is an illegal drug of abuse usually consumed by adolescents in a socio-economically vulnerable situation. Repeated drug use targets key brain circuits disrupting the processes that underlie emotions and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate-early genes (IEGs). Nevertheless, changes in transcriptional regulation associated with CBP consumption remain unknown. OBJECTIVES: We aimed to describe behavioral phenotype related to locomotion, anxiety-like behavior, and memory of CBP-injected mice and to study IEGs expression after an abstinence period. METHODS: Five-week-old female CF-1 mice were i.p. injected daily with vehicle or CBP (40 mg/kg) for 10 days and subjected to a 10-day period of abstinence. Open field and novel object recognition tests were used to evaluate locomotion and anxiety-like behaviors and recognition memory, respectively, during chronic administration and after abstinence. After abstinence, prefrontal cortex (mPFC) and nucleus accumbens (NAc) were isolated and gene expression analysis performed through real-time PCR. RESULTS: We found an increase in locomotion and anxiety-like behavior during CBP administration and after the abstinence period. Furthermore, the CBP group showed impaired recognition memory after abstinence. Egr1, FosB, ΔFosB, Arc, Bdnf, and TrkB expression was upregulated in CBP-injected mice in NAc and FosB, ΔFosB, Arc, and Npas4 expression was downregulated in mPFC. We generated an anxiety score and found positive and negative correlations with IEGs expression in NAc and mPFC, respectively. CONCLUSION: Our results suggest that chronic CBP exposure induced alterations in anxiety-like behavior and recognition memory. These changes were accompanied by altered IEGs expression.

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Consolidated memories can return to a labile state upon presentation of a reminder, followed by a period of re-stabilization known as reconsolidation. This period can take several hours, and if an amnesic agent (e.g. new learning) is administered inside the time window of reconsolidation (when the memory is still labile) the memory is impaired, whereas the memory remains unaffected if the amnesic agent is administered outside this time window. Sleep plays a fundamental role in the consolidation and integration of new memories, and recently sleep has also been implicated in memory reconsolidation. Here, we studied the role of sleep in accelerating the reconsolidation time window. On day 1, participants learned a list of syllable-pairs (List 1). On day 2, they received a reminder, followed by interference learning (List 2) administered either after 90 min of wakefulness, after 90 min of sleep, or after 10 h of wakefulness. On day 3, participants had to recall List 1 first, followed by List 2, and we assessed the Retrieval-Induced-Forgetting Effect (RIF) on List 2 as a measure of List 1 memory stability. We found that the 90 min sleep group showed an intact RIF effect similar to the 10 h wake group, reflecting stable List 1 memory after 90 min of sleep and after 10 h of wakefulness. However, the RIF effect was absent after 90 min of wakefulness, suggesting that the List 1 memory was still labile at that time. Moreover, the RIF effect in the 90 min sleep group was associated with power density in the slow oscillation frequency band (0.5-1 Hz) during SWS and S2. These findings suggest that 90 min of sleep accelerate memory re-stabilization after reminder presentation, shortening the reconsolidation time window and protecting the memory against subsequent interference. This rapid memory re-stabilization may depend on slow oscillation activity during NREM sleep.

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Consolidated memory can be again destabilized by the presentation of a memory cue (reminder) of the previously acquired information. During this process of labilization/restabilization memory traces can be either impaired, strengthened or updated in content. Here, we study if a consolidated memory can be updated by linking one original cue to two different outcomes and whether this process was modulated by the GABAergic system. To aim that, we designed two experiments carried out in three consecutive days. All participants learned a list of non-sense syllable pairs on day 1. On day 2 the new information was introduced after the reminder or no-reminder presentation. Participants were tested on day 3 for the updated or original list (Exp. 1). In Exp. 2 we tested whether this new information was incorporated by an inhibitory process mediated by the GABAergic system. For that, participants retrieved the original information before being taken Clonazepam 0.25mg (GABAA agonist) or Placebo pill. We found that the groups that received the reminder correctly recalled the old and new information. However, the no reminder groups only correctly recalled the original information. Furthermore, when testing occurred in the presence of Clonazepam, the group that received the reminder plus the new information showed an impaired original memory performance compared to the group that received only Clonazepam (without reminder) or the reminder plus Placebo pill. These results show that new information can be added to a reactivated declarative memory in humans by linking one cue to two different outcomes. Furthermore, we shed light on the mechanisms of memory updating being the GABAergic system involved in the modulation of the old and new information expression.

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Resumen: La memoria tipo episódica (MTE) implica recordar de manera integrada el qué, el dónde y el cuándo de un evento y es atribuible a animales y humanos, permitiendo recordar y actualizar lo aprendido. Se realizó un experimento para estudiar la actualización y recuerdo integrado en la MTE de niños prescolares. Se compararon dos condiciones (A=B y A>B) que involucraron más de dos fases en las que varió la magnitud para una de las consecuencias. En una primera fase ambas condiciones presentaron la misma información (A+, B+ y C+), mientras que las fases subsecuentes se presentaron diferentes magnitudes de consecuencia (segunda fase: A++++ o A**** de acuerdo a la condición; tercera fase: B++++). Finalmente, la prueba ocurrió 24 h después del entrenamiento y los participantes eligieron entre el contenedor A o B. El qué fue la consecuencia; el dónde, los contenedores, y el cuándo, el orden de cada fase presentada. Los datos sugieren que tras el paso del tiempo los participantes recuerdan de manera integrada el qué, el dónde y el cuándo actualizando el aprendizaje de cada experiencia. Los participantes consideraron la magnitud de la consecuencia obtenida en cada fase, mostrando así la flexibilidad del recuerdo propuesta por la MTE. Los datos son coherentes con las predicciones de la Regla de Ponderación Temporal de Devenport.

Abstract: Episodic-like memory (ELM) involves that animals can remember What, Where and When about an event and it is attributable to animals and humans, this ability permits recall and update learning. One experiment was made for study the update and integrated recall of ELM in preschoolers. We compared two conditions (A = B and A > B) that involve more than two phases with modifying of one magnitude outcome. In the first phase, both conditions had the same information, while next phases had different outcome value in two containers (A or B). Finally, a test was presented after 24 hours: participants chose between A or B container. What, was the outcome subjective value; Where, was the containers and When was the order to each phase. Data suggest that after time pass, participants remember an integrated way about What, Where and When. Even when participants update learning for each experience participants chose according to time and outcome subjective value of each phase and the information retrieval is flexible as happen with ELM. Results are consistent with predictions of Devenport's Temporal Weighting Rule.

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The reconsolidation process is the mechanism by which the strength and/or content of consolidated memories are updated. This process is triggered by the presentation of a reminder (training cues). It is not always possible to trigger the reconsolidation process. For example, memory age and strength are boundary conditions for the reconsolidation process. Here, we investigated the dynamic changes in these conditions. We propose that the boundary conditions of the reconsolidation process are not fixed and vary as a consequence of the interaction between memory features and reminder characteristics. To modify memory properties, participants received a threatening social protocol that improves memory acquisition or a control condition (fake, without social interaction) prior to learning pairs of meaningless syllables. To determine whether a strong young or old declarative memory undergoes the reconsolidation process, we used an interference task (a second list of pairs of meaningless syllables) to disrupt memory re-stabilization. To assess whether the older memory could be strengthened, we repeated the triggering of reconsolidation. Strong young or old memories modulated by a threatening experience could be interfered during reconsolidation and updated (strengthened) by reconsolidation. Rather than being fixed, boundary conditions vary according to the memory features (strong memory), which indicates the dynamic nature of the reconsolidation process. Our findings demonstrate that it is possible to modify these limits by recruiting the reconsolidation process and making it functionally operative again. This novel scenario opens the possibility to new therapeutically approaches that take into account the reconsolidation process.

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Following the presentation of a reminder, consolidated memories become reactivated followed by a process of re-stabilization, which is referred to as reconsolidation. The most common behavioral tool used to reveal this process is interference produced by new learning shortly after memory reactivation. Memory interference is defined as a decrease in memory retrieval, the effect is generated when new information impairs an acquired memory. In general, the target memory and the interference task used are the same. Here we investigated how different memory systems and/or their valence could produce memory reconsolidation interference. We showed that a reactivated neutral declarative memory could be interfered by new learning of a different neutral declarative memory. Then, we revealed that an aversive implicit memory could be interfered by the presentation of a reminder followed by a threatening social event. Finally, we showed that the reconsolidation of a neutral declarative memory is unaffected by the acquisition of an aversive implicit memory and conversely, this memory remains intact when the neutral declarative memory is used as interference. These results suggest that the interference of memory reconsolidation is effective when two task rely on the same memory system or both evoke negative valence.

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Memories can be altered by negative or arousing experiences due to the activation of the stress-responsive sympatho-adrenal-medullary axis (SYM). Here, we used a neutral declarative memory that was acquired during multi-trial training to determine the effect of a threatening event on memory without emotional valence. To this end, participants received a new threatening social protocol before learning pairs of meaningless syllables and were tested either 15 min, 2 days or 8 days after acquisition. We first demonstrated that this threatening social situation activates not only the SYM axis (Experiment 1) and the hypothalamus-pituitary-adrenal axis (HPA; Experiment 2), but also, it improves the acquisition or early consolidation of the syllable pairs (Experiment 3). This improvement is not a transient effect; it can be observed after the memory is consolidated. Furthermore, this modulation increases the persistence of memory (Experiment 4). Thus, it is possible to affect memories with specific events that contain unrelated content and a different valence.

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Se evaluó el efecto de 0, 0.035, 0.150, 0.300 g de alcohol sobre 2 componentes de la memoria explícita o declarativa, en 16 participantes, hombres y mujeres, mediante la aplicación de la prueba de textos del Weschler-III (WMS-III), utilizando un diseño factorial 2 x 4 de medidas repetidas contrabalanceadas. No se encontraron diferencias entre los sexos, pero sí entre las dosis, siendo 0.150 g de alcohol/kg de peso corporal la que más decrementó el recuerdo de episodios y de temas, especialmente a mediano plazo, con tamaños de los efectos de 43.9 y 62.9 %, respectivamente. Estos resultados confirman que el alcohol, aun en dosis bajas, deteriora más el componente semántico del recuerdo explícito, aproximadamente media hora después de su consumo.

This study assessed the effect of low doses of alcohol (0, 0.035, 0.150, 0.300 g) on two elements of explicit or declarative memory, in 16 participants, 8 women and 8 men, with The Weschler Memory Scale III Text Test. A factorial 2 * 4 counterbalanced with repeated measures design was used. There were no statistically significant differences by gender, but there were differences among doses, specially 0.150 g / kg., which reduced episodic and semantic retrieval, between 43.9 and 62.9 % of effect strength, in intermediate term memory. These results provided evidence that alcohol in low doses has a more pronounced effect in semantic, rather than episodic memory, in the middle term.

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Introducción: Diferentes niveles de “alertamiento” emocional pueden favorecer la potenciación o el deterioro de la memoria. El impacto emocional en personas víctimas del desplazamiento en Colombia puede constituirse en un factor de riesgo para el desarrollo del trastorno por estrés postraumático (TEPT). Objetivo: Evaluar la memoria emocional de sujetos en condición de desplazamiento por la violencia con y sin diagnóstico positivo para el TEPT. Método: Muestra de 95 voluntarios en condición de desplazamiento del área metropolitana de Bucaramanga (18 a 61 años), a quienes se les aplicaron los instrumentos de diagnóstico para TEPT (DSM IV, Checklist) y una prueba auditivo-visual de memoria emocional. Los participantes fueron distribuidos en dos grupos: sujetos con TEPT y sujetos sin TEPT. Ambos grupos fueron redistribuidos en cuatro subgrupos según la versión neutra y emocional de la prueba auditivo-visual. Resultados: El grupo de participantes clasificado con TEPT atribuyó Una mayor ponderación a la historia emocional, pero su contenido “alertador” no potenció la memoria de estos participantes. Conclusión: El contenido “alertante” de la prueba auditivo visual no potenció la memoria de aquellos sujetos diagnosticados con TEPT, lo cual sugiere que estos participantes pueden presentar un deterioro de las potencialidades mnemónicas dado por las limitaciones funcionales que involucran los procesos de reforzamiento emocional...

Introduction: Different levels of emotional arousal can potentiate or impair memory. Since the emotional impact on victims of displacement in Colombia may constitute a risk factor for the development of post-traumatic stress disorder (PTSD), the objective of this study was to evaluate emotional memory of people displaced by violence with and without PTSD. Method: The sample consisted of 95 volunteers in condition of displacement of the metropolitan area of Bucaramanga (18 to 61 years old), to whom an instrument for the diagnosis of PTSD (DSM IV, Checklist) and An audio-visual Emotional Memory Test were applied. The participants were distributed into two groups: Subjects with and without PTSD. Both groups were redistributed into four subgroups according with the emotional or neutral version of the emotional memory test. Results: The group of participants with PTSD attributed an emotional rate higher to the emotional story than to the neutral story, but the emotional arousal content did not potentiate the memory of these participants. Conclusion: The emotional contents implemented in this emotional memory test did not potentiate the memory of subjects diagnosed with PTSD. Based on this, it could be that these participants present a deterioration of the mnemonic potential given by the functional limitations that involve the processes of emotional reinforcement...

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Emotional content/context enhances declarative memory through modulation of encoding and retrieval mechanisms. At encoding, neurophysiological data have consistently demonstrated the subsequent memory effect in theta and gamma oscillations. Yet, the existing studies were focused on the emotional content effect and let the emotional context effect unexplored. We hypothesized that theta and gamma oscillations show higher evoked/induced activity during the encoding of visual stimuli when delivered in an emotionally arousing context. Twenty-five healthy volunteers underwent evoked potentials (EP) recordings using a 21 scalp electrodes montage. They attended to an audiovisual test of emotional declarative memory being randomly assigned to either emotionally arousing or neutral context. Visual stimulus presentation was used as the time-locking event. Grand-averages of the EP and evoked spectral perturbations were calculated for each volunteer. EP showed a higher negative deflection from 80 to 140 ms for the emotional condition. Such effect was observed over central, frontal and prefrontal locations bilaterally. Evoked theta power was higher in left parietal, central, frontal, and prefrontal electrodes from -50 to 300 ms in the emotional condition. Evoked gamma power was higher in the emotional condition with a spatial distribution that overlapped at some points with the theta topography. The early theta power increase could be related to expectancy induced by auditory information processing that facilitates visual encoding in emotional contexts. Together, our results suggest that declarative memory enhancement for both emotional content and emotional context are supported by similar neural mechanisms at encoding, and offer new evidence about the brain processing of relevant environmental stimuli.

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Long-term potentiation (LTP) is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a) memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; b)hippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex) are also necessary for memory formation of the one-trial task, and perhaps of many others.

A potenciação de longa duração (LTP) é o aumento de respostas pós-sinápticas durante horas, dias ou semanas após a breve estimulação repetitiva de aferentes pre-sinápticos. Foi proposto durante 30 anos ser a base da memória de longa duração. Vários achados recentes finalmente apoiaram esta hipótese: a) a formação da memória de esquiva inibitória adquirida numa sessão depende de uma cadeia de processos moleculares na região CA1 do hipocampo quase idêntica à da LTP nessa mesma região; b) LTP hipocampal nessa região acompanha a formação da memóría dessa tarefa e de outra semelhante. No entanto, a LTP de CA1 e os processos de memória podem ser dissociados e, fora disso, processos plásticos em outras regiões cerebrais (amígdala, córtex entorrinal, córtex parietal) também são necessários para a formação da memória da tarefa de uma sessão e talvez de muitas outras.

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