Neurobiological mechanisms of conditioned fear memory reconsolidation / 中国病理生理杂志

Post-traumatic stress disorder (PTSD) is a reactive mental disorder that occurs after an individual was exposed to a traumatic event,and the core of the treatment is the extinction of conditioned fear memory caused by stress.Fear memory is an incentive mechanism based on external stimuli that occupy a central position in the defense system.Traditional memory concept convinced that the original memory traces were in an unstable state when the memory was activated.This process is called memory reconsolidation.The research has proved the existence of the fear memory reconsolidation,but the specific mechanism of reconsolidation has not been clarified.The animal studies show that many brain sites and molecular mechanisms are involved in the process of fear memory reconsolidation.Understanding the underlying mechanisms of fear memory reconsolidation is conducive to the treatment of specific phobias and PTSD.This review summarized the brain structure and molecular mechanism of conditioned fear memory reconsolidation,providing a new direction for the in-depth study of conditioned fear memory reconsolidation and PTSD.

Neurobiological mechanisms of conditioned fear memory reconsolidation / 中国病理生理杂志

Post-traumatic stress disorder (PTSD) is a reactive mental disorder that occurs after an individual was exposed to a traumatic event,and the core of the treatment is the extinction of conditioned fear memory caused by stress.Fear memory is an incentive mechanism based on external stimuli that occupy a central position in the defense system.Traditional memory concept convinced that the original memory traces were in an unstable state when the memory was activated.This process is called memory reconsolidation.The research has proved the existence of the fear memory reconsolidation,but the specific mechanism of reconsolidation has not been clarified.The animal studies show that many brain sites and molecular mechanisms are involved in the process of fear memory reconsolidation.Understanding the underlying mechanisms of fear memory reconsolidation is conducive to the treatment of specific phobias and PTSD.This review summarized the brain structure and molecular mechanism of conditioned fear memory reconsolidation,providing a new direction for the in-depth study of conditioned fear memory reconsolidation and PTSD.

A labilidade do conhecimento adquirido: gênese e renascimento dos estudos sobre o efeito de reconsolidação / La labilité des connaissances acquises: études de la genèse et de la renaissance sur l'effet de la reconsolidation / La labilidad del conocimiento adquirido: la génesis y el renascimento de los estúdios sobre el efecto de reconsolidación / The lability of the acquired knowledge: genesis and rebirth of the studies on the effect of reconsolidation

Um robusto conjunto de evidências demonstra que, após a reativação, as memórias incorrem em um estado de labilidade, durante o qual são suscetíveis a manipulações que interferem em seu conteúdo ou na probabilidade de recuperação no futuro. Esse efeito, denominado "reconsolidação", é similar ao período de instabilidade que se segue ao aprendizado de uma nova informação, classicamente referido como "consolidação". Embora o efeito de reconsolidação seja conhecido já há mais de 40 anos, apenas recentemente o tema recebeu notoriedade, e desde então um crescente número de publicações científicas tem elucidado alguns dos seus processos fundamentais. Porém, uma vez que o tema tem sido pouco divulgado na literatura nacional, este artigo apresenta uma revisão crítica de literatura, na qual se discutem os antecedentes históricos do conceito de reconsolidação, seus métodos de investigação, sua abrangência e as perspectivas de pesquisa.

A robust set of evidence demonstrates that, after reactivation, the memories incur a lability state, during which they are susceptible to manipulations that interfere in its content or on the probability of retrieval in the future. This effect, called "reconsolidation", is similar to the period of instability following the learning of new information, classically referred to as a "consolidation". Although the effect of reconsolidation is known for more than 40 years, the topic only received notoriety recently, and since then, an increasing number of scientific publications has elucidated some of the fundamental processes. However, once the theme has been little reported in the Brazilian literature, this article presents a critical review of the literature, which discuss the historical background of the reconsolidation concept, its methods of investigation, scope and prospects for research.

Un cuerpo sólido de evidencias demuestra que después de la reactivación, las memorias incurren en un estado de labilidad, y durante este período son susceptibles a manipulaciones que interfieren en su contenido, o en la probabilidad de su futura recuperación. Este efecto, denominado "reconsolidación", es similar al período de inestabilidad que tiene lugar después del aprendizaje de una nueva información (lo que se denomina clasicamente "período de consolidación"). Aunque el efecto de reconsolidación se conoce desde hace más de 40 años, sólo recientemente este tema recibió notoriedad. A partir de entonces, un número creciente de publicaciones científicas ha lanzado luz sobre algunos de sus procesos fundamentales. Sin embargo, como el tema ha recibido poca atención en la literatura científica portuguesa, en este manuscrito presentamos una revisión critica de la literatura, y se discuten las raíces históricas del concepto de reconsolidación, los métodos de investigación, así como las direcciones futuras de la investigación sobre el tema.

Un corps robuste de preuves démontre que, après la réactivation, les souvenirs encourent un état d'instabilité, au cours de laquelle ils sont sensibles aux manipulations qui interfèrent avec leur contenu ou de la probabilité de recouvrement. Cet effet, appelé "reconsolidation" est similaire au période d'instabilité que suit l'apprentissage d'une nouvelle information, classiquement appelé de "consolidation" . Bien que l'effet de la reconsolidation soit connu depuis plus de 40 ans, ce ne fut que récemment que la question reçue notoriété, et, depuis lors, un nombre croissant de publications scientifiques ont élucidé certains de ses processus clés. Néanmoins. dés que le sujet a mérité peu d'attention dans la littérature nationale, ce document présente une revue critique de la littérature, où nous discutons l'histoire de la notion de reconsolidation, et des méthodes d'enquête, son champ d'application et perspectives de recherche.

Memory retrieval-extinction paradigm and its application on drug addicts / 中华行为医学与脑科学杂志

Based on the traditional fear extinction training paradigm, the retrieval-extinction para-digm rewrites fear memory within the reconsolidation window,and reduces their fear response by decreasing the valence of fear stimulus. From the perspective of psychology,the main reason of addicts relapse is that the intensive memory of the painful experience inspired when protracted withdrawal symptoms of drug depend-ence. The reduction of the sensitivity of drug related memory, which is the key of drug detoxification is to change the memory caused by drug related cues. The retrieval-extinction paradigm provides no drug treatment and a new non-invasive model for addicts,and a new perspective to reduce the relapse rate,and to improve the quality of life of addicts. We can do empirical research which using memory retrieval-estinction paradigm on drug addicts in the future.The memory retrieval paradigm can be applied to empirical research in drug ad-dicts in future.

Drug reward memory:implication from drug-induced conditioned place preference model / 中国药理学与毒理学杂志

Drug addiction is a chronic,relapsing brain disorder,which develops,in part,because of aberrant learning and memory. Accumulative studies during recent decades demonstrated that addictive drug hijacks the normal memory circuit in the brain to form a long-lasting drug reward memory,which determines relapse to addictive drug. In this review,we will describe what has been learned about drug reward memory,especially focused on one of the associative drug reward memory models,drug-induced conditioned place preference. Drug reward memory is a dynamic process,which consists of several stages,including acquisition,consolidation,maintenance,retrieval,reconsolidation and extinction. Interventions with pharmacological in these memory processes will differentially regulate drug reward memory. Furthermore , the recently developed novel pure behavioral procedure according to the hypothesis of memory processes,e.g. post-retrieval extinction,could erase drug reward memory,which shows more advantages than the pharmacological medications that used in memory studies. Finally, we discussed two major methodological issues in drug reward memory,procedure and timing,which should be carefully considered when designing the related studies and interpreting the results from related studies. So far,it is not sure whether it is feasible to develop a pharmacological medication that only erases drug reward memory without impairing normal memories,we propose that inhibition of drug reward memory would be a good strategy to limit the risk of relapse to addictive drug. Although current findings on drug reward memory benefits little for treatment of drug addiction,the ongoing studies on drug reward memory will provide a promising strategy for reducing the risk of relapse to addictive drug.

Intervención sobre el mecanismo de reconsolidación / Intervention on the Reconsolidation Mechanism

En la actualidad, existen tratamientos eficaces para reducir los síntomas de ansiedad y el malestar asociado. Sin embargo, se observa con frecuencia que las respuestas de ansiedad, después de haberse extinguido, se recuperan, sin que esté claro el mecanismo que subyace a dicha recuperación. Desde hace décadas, se considera la posibilidad de un mecanismo de reconsolidación que colaboraría en el proceso de almacenar nuevamente los recuerdos que han sido evocados. Algunas investigaciones recientes revelan que la intervención sobre el mecanismo de reconsolidación aparentemente previene la recuperación de respuestas de ansiedad que han sido previamente extinguidas. Si esto es así, podría ser una alternativa a los tratamientos actuales de los trastornos de ansiedad basados en la exposición. El objetivo del presente trabajo es revisar la evidencia sobre los efectos de actuar sobre el mecanismo de reconsolidación para la reducción de las respuestas de ansiedad. Finalmente se discuten las posibles implicaciones clínicas.

At the present, effective treatments are available to reduce anxiety symptoms and their associated distress. Nevertheless, it is frequently observed that anxiety responses are recovered after extinction, without being clear the responsible mechanism of such phenomenon. For decades, it has been presumed the existence of a reconsolidation mechanism. Such mechanism is thought to participate in the re-storage of memories that have been evoked. Recent research apparently reveals that intervention on reconsolidation mechanisms prevents the recovery of anxiety responses that have been previously extinguished. Intervention on these mechanisms could represent an alternative to current psychological treatments for anxiety disorders based on exposure procedures. The objective of the present work is to review the evidence on reconsolidation mechanisms and its effects on the reduction of anxiety responses. Finally some clinical implications will be discussed.

O après-coup e a reconsolidação da memória / The après-coup and reconsolidation of memory / L'après-coup et la reconsolidation de la mémoire / El après-coup y la reconsolidación de la memoria

Em diferentes áreas do conhecimento é reconhecido que a memória está sujeita a transformações ao longo do tempo. Partindo desse pressuposto, o objetivo do presente estudo é apresentar uma discussão compreendendo a ideia de que nossas recordações são suscetíveis a transformações e a concepção de après-coup. Há o delineamento de algumas ideias acerca da temporalidade em Psicanálise e do mecanismo de reconsolidação da memória segundo as Neurociências. Utilizando-se tais conceitos, evidenciou-se a viabilidade de se pensar uma interlocução entre a Psicanálise e as Neurociências.

Over time, it is recognized that the memory is subject to changes in different fields of knowledge. Based on this assumption, the objective of this study is to present a discussion comprising the idea that our memories are susceptible to changes and to the conception of après-coup. There is the outline of some ideas about the temporality in psychoanalysis and the memory reconsolidation mechanism according to neurosciences. It was demonstrated the feasibility of considering a dialogue between psychoanalysis and neurosciences, using such concepts.

Dans les différents domaines de la connaissance est reconnu que la mémoire est susceptible de changer au fil du temps. Sur la base de cette hypothèse, l'objectif de cette étude est de présenter une discussion comprenant l'idée que nos souvenirs sont susceptibles d'évoluer et la conception d'après-coup. Il sont décrivées des idées sur la temporalité en psychanalyse et le mécanisme de reconsolidation de la mémoire selon les neurosciences. L'utilisation de ces concepts démontre la faisabilité de l'examen d'un dialogue entre la Psychanalyse et les Neurosciences.

En diferentes áreas del conocimiento es reconocido que la memoria está sujeta a cambios en el tiempo. Con base en este supuesto, el objetivo del presente estudio es presentar una discusión comprendiendo la idea de que nuestros recuerdos son susceptibles de cambiar y el diseño de après-coup. A partir de eso, hay el delineamiento de algunas ideas acerca de la temporalidad en Psicoanálisis y del mecanismo de reconsolidación de la memoria según las Neurociencias. Se evidenció la viabilidad de considerar un diálogo entre el Psicoanálisis y las Neurociencias, en el uso de tales conceptos.

Effect of Intensity of Unconditional Stimulus on Reconsolidation of Contextual Fear Memory

Memory reconsolidation is ubiquitous across species and various memory tasks. It is a dynamic process in which memory is modified and/or updated. In experimental conditions, memory reconsolidation is usually characterized by the fact that the consolidated memory is disrupted by a combination of memory reactivation and inhibition of protein synthesis. However, under some experimental conditions, the reactivated memory is not disrupted by inhibition of protein synthesis. This so called "boundary condition" of reconsolidation may be related to memory strength. In Pavlovian fear conditioning, the intensity of unconditional stimulus (US) determines the strength of the fear memory. In this study, we examined the effect of the intensity of US on the reconsolidation of contextual fear memory. Strong contextual fear memory, which is conditioned with strong US, is not disrupted by inhibition of protein synthesis after its reactivation; however, a weak fear memory is often disrupted. This suggests that a US of strong intensity can inhibit reconsolidation of contextual fear memory.

Treatment of fear memories: interactions between extinction and reconsolidation

Retrieval labilizes memory traces and these gates two protein synthesis-dependent processes in the brain: extinction, which inhibits further retrieval, and reconsolidation, which may enhance retrieval or change its content. Extinction may itself suffer reconsolidation. Interactions among these processes may be applied to treatments of fear memories, such as those underlying post-traumatic stress disorders.

A evocação labiliza os arquivos de memória, e isto permite dois processos dependentes de síntese protéica no cérebro: a extinção, que inibe a evocação ulterior, e a reconsolidação, que pode aumentar a evocação ou mudar seu conteúdo. A extinção pode por sua vez sofrer reconsolidação. Interações entre estes dois processos podem ser aplicados ao tratamento das memórias de medo, tais como aquelas em que se baseia o estresse pós-traumático.

Neural Circuit and Mechanism of Fear Conditioning

Pavlovian fear conditioning has been extensively studied for the understanding of neurobiological basis of memory and emotion. Pavlovian fear conditioning is an associative memory which forms when conditioned stimulus (CS) is paired with unconditioned stimulus (US) once or repeatedly. This behavioral model is also important for the understanding of anxiety disorders such as posttraumatic stress disorder. Here we describe the neural circuitry involved in fear conditioning and the molecular mechanisms underlying fear memory formation. During consolidation some memories fade out but other memories become stable and concrete. Emotion plays an important role in determining which memories will survive. Memory becomes unstable and editable again immediately after retrieval. It opens the possibility for us of modulating the established fear memory. It provides us with very efficient tools to improve the efficacy of cognitive-behavior therapy and other exposure-based therapy treating anxiety disorders.

Pharmacological effects and behavioral interventions on memory consolidation and reconsolidation

In this article, we will review some behavioral, pharmacological and neurochemical studies from our laboratory on mice, which might contribute to our understanding of the complex processes of memory consolidation and reconsolidation. We discuss the post-training (memory consolidation) and post-reactivation (memory reconsolidation) effects of icv infusions of hemicholinium, a central inhibitor of acetylcholine synthesis, of intraperitoneal administration of L-NAME, a non-specific inhibitor of nitric oxide synthase, of intrahippocampal injections of an inhibitor of the transcription factor NF-κB, and the exposure of mice to a new learning situation on retention performance of an inhibitory avoidance response. All treatments impair long-term memory consolidation and retrieval-induced memory processes different from extinction, probably in accordance with the "reconsolidation hypothesis".