Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice / 神经科学通报·英文版

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.

Simvastatin Blocks Reinstatement of Cocaine-induced Conditioned Place Preference in Male Mice with Brain Lipidome Remodeling / 神经科学通报·英文版

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.

SNP-SNP interactions in the BDNF, COMT, CBR1 and CCK genes, associated with post-traumatic stress disorder in urban residents of Itagüí, Colombia / Interacciones SNP-SNP en los genes BDNF, COMT, CBR1 y CCK asociadas al trastorno de estrés postraumático en la población urbana de Itagüí, Colombia

Abstract Introduction: Single nucleotide polymorphisms (SNPs) in the BDNF, COMT, CBR1 and CCK genes have been associated with the process of fear extinction in humans. Since fear extinction plays a key role in recovering from psychological trauma, there is a possibility that these genes modulate the risk of developing post-traumatic stress disorder (PTSD). Objective: To assess unilocus and multilocus associations between SNPs in the BDNF, COMT, CBR1 and CCK genes and the risk of developing PTSD. Materials and methods: 129 inhabitants of the municipality of Itagüí, Colombia, who had experienced psychological trauma at least once, were genotyped for these polymorphisms (38 cases of PTSD and 91 controls). Logistic regression was used to perform unilocus and multilocus association tests for single SNPs and existing SNP-SNP genotypic combinations. Results: No unilocus associations were found, but interactions between the BDNF and CBR1 genes and between the COMT and CCK genes were observed. Of these interactions, the genotypic combinations that behaved as risk factors were AG-AA (OR=13.52, p<0.05) in the BDNF-CBR1 interaction, and TC-AA (OR=13.70, p<0.05) in the CCK-COMT interaction. Conclusions: The two pairs of interacting polymorphisms found in this study could act additively and generate a greater risk of developing PTSD after suffering psychological trauma. People who have a single allele have a lower risk of developing PTSD than those who have two alleles in the interacting genes.

Resumen Introducción. Los polimorfismos de un solo nucleótido (SNP, por su sigla en inglés) en los genes BDNF, COMT, CBR1 y CCK han sido asociados con el proceso de extinción del miedo en humanos. Dado que la extinción del miedo es clave para la recuperación del trauma psicológico, es posible que estos genes modulen el riesgo de desarrollar trastorno de estrés postraumático (TEPT). Objetivo. Evaluar las asociaciones unilocus y multilocus entre los SNP en los genes BDNF, COMT, CBR1 y CCK y el riesgo de desarrollar TEPT. Materiales y métodos. 129 habitantes del municipio de Itagüí, Colombia, que habían experimentado trauma psicológico al menos una vez, fueron genotipificados para estos polimorfismos (38 casos de TEPT y 91 controles). Se realizaron pruebas de asociación unilocus y multilocus por regresión logística para SNP únicos y las combinaciones genotípicas SNP-SNP existentes. Resultados. No se encontraron asociaciones unilocus, pero se observaron interacciones entre BDNF y CBR1, y CCK y COMT. De estas interacciones, las combinaciones genotípicas que se comportaron como factores de riesgo fueron AG-AA (OR=13.52, p<0.05) de BDNF-CBR1 y TC-AA (OR=13.70, p<0.05) de CCK-COMT. Conclusiones: Los dos pares de polimorfismos en interacción encontrados en el presente estudio podrían actuar de forma aditiva y generar un mayor riesgo de desarrollar TEPT después de sufrir trauma psicológico. Quienes portan un solo alelo tienen un menor riesgo de desarrollar el trastorno que quienes portan dos alelos en genes que interactúan entre sí.

Standardization of the face-hand test in a Brazilian multicultural population: prevalence of sensory extinction and implications for neurological diagnosis

OBJECTIVE: The face-hand test is a simple, practical, and rapid test to detect neurological syndromes. However, it has not previously been assessed in a Brazilian sample; therefore, the objective of the present study was to standardize the face-hand test for use in the multi-cultural population of Brazil and identify the sociodemographic factors affecting the results. METHODS: This was a cross sectional study of 150 individuals. The sociodemographic variables that were collected included age, gender, race, body mass index and years of education. Standardization of the face-hand test occurred in 2 rounds of 10 sensory stimuli, with the participant seated to support the trunk and their vision obstructed in a sound-controlled environment. The face-hand test was conducted by applying 2 rounds of 10 sensory stimuli that were applied to the face and hand simultaneously. The associations between the face-hand test and sociodemographic variables were analyzed using Mann-Whitney tests and Spearman correlations. Binomial models were adjusted for the number of face-hand test variations, and ROC curves evaluated sensitivity and specificity of sensory extinction. RESULTS: There was no significant relationship between the sociodemographic variables and the number of stimuli perceived for the face-hand test. There was a high relative frequency of detection, 8 out of 10 stimuli, in this population. Sensory extinction was 25.3%, which increased with increasing age (OR=1.4[1:01–1:07]; p=0.006) and decreased significantly with increasing education (OR=0.82[0.71-0.94]; p=0.005). CONCLUSION: In the Brazilian population, a normal face-hand test score ranges between 8–10 stimuli, and the results indicate that sensory extinction is associated with increased age and lower levels of education.

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.

Changes of telemetry electrical activity in the infralimbic cortex of morphine-dependent rats with extinguished drug-seeking behavior / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior.</p><p><b>METHODS</b>SD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system.</p><p><b>RESULTS</b>In rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased β wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and β wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased β wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and β wave compared with those in the withdrawal period.</p><p><b>CONCLUSION</b>Morphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.</p>

The influence of sex and menstrual cycle on conditioned acquisition and extinction: Event-related potential research / 生理学报

Previous studies have indicated phase-related differences in conditioned acquisition and extinction. In recent years, many researchers used event-related potential (ERP) technology to assess the extent of the acquisition and extinction. Therefore, this study was aimed to assess the sex- and menstrual cycle-dependent effects on the conditioned acquisition and extinction using ERP technology. Thirty-two females at two phases (menses phase, FM, and luteal phase, FL) of their menstrual cycle and 16 males participated in the experiment. The experiment consisted of two stages: acquisition stage and extinction stage. In the acquisition stage, in the predictable context, a condition stimulus (CS) was always followed by the presentation of a negative picture or a neutral picture; but in the unpredictable context, a CS was paired with a negative picture or a neutral picture 20% of the time. In the extinction stage, only CS was presented. The results showed that at acquisition stage, significant larger P2 amplitudes were recorded in female subjects in FL and FM in comparison with those of males. The female subjects in FL may acquire the strongest CS-US conditional connection. At extinction stage, the female subjects in FL showed larger P2 amplitudes than males, but there were no significant differences in P2 amplitudes between the males and females in FM. The results suggest that the females in FL allocate more attention resources to the acquisition of a conditioned response and delayed extinction. In conclusion, we suggest that female menstrual cycle may modulate conditioned acquisition and extinction processes, and our ERP data may provide an explanation for the premenstrual dysphoric disorder.

New frontiers in the study of memory mechanisms

We review recent work on three major lines of memory research: a) the possible role of the protein kinase M-zeta (PKMzeta) in memory persistence; b) the processes of “synaptic tagging and capture” in memory formation; c) the modulation of extinction learning, widely used in the psychotherapy of fear memories under the name of “exposure therapy”. PKMzeta is a form of protein kinase C (PKC) that apparently remains stimulated for months after the consolidation of a given memory. Synaptic tagging is a mechanism whereby the weak activation of one synapse can tag it with a protein so other synapses in the same cell can reactivate it by producing other proteins that bind to the tag. Extinction, once mistakenly labeled as a form of forgetting, is by itself a form of learning; through it animals can learn to inhibit a response. We now know it can be modulated by neurotransmitters or by synaptic tagging, which should enable better control of its clinical use.

Comparative proteomic analysis of the nucleus accumbens during extinction and reinstatement of morphine dependence / Análisis proteómico comparativo del núcleo accumbens durante laextinción y recaída de la dependencia a la morfina

BACKGROUND: The aim of this study was to detect differentially expressed proteins in the nucleus accumbens between the states of extinction and reinstatement of morphine addiction. Numerous studies on the neurobiological mechanisms concerning drug craving and relapse have been reported to date, but data on their relationship with the underlying key molecular mechanisms involved remain limited. METHODS: In this study, 40 male SpragueDawley rats were equally randomized into a saline group and a morphine group. Both groups received drug selfadministration training, after which extinction models were established naturally. The groups were further divided into two subgroups for extinction and reinstatement tests. Cerebral nucleus accumbens masses were measured for total protein extraction. Twodimensional electrophoresis was performed to determine differential protein spots. These differential proteins were then enzymolysed and identified using mass spectrography. RESULTS: The proteins were classified as fatty acidbinding protein, serine/threonine protein phosphatase 2A catalytic subunit beta isoform, serine/threonine protein phosphatase 2A catalytic subunit alpha isoform, serine/threonine protein phosphatase 2A regulatory subunit B² subunit gamma or heat shock protein 90 cochaperone CDC37. CONCLUSION: Significant changes in five proteins were detected between extinction and reinstatement. These proteins are correlated with phosphorylation and the tricarboxylic acid cycle.

ANTECEDENTES: El objetivo de este estudio fue detectar las proteínas diferencialmente expresadas en el núcleo accumbens entre los estados de extinción y recaída de la adicción a la morfina. Hasta la fecha se han reportado numerosos estudios en relación con los mecanismos neurobiológicos del deseo incontenible y recaída en el consumo de drogas, pero los datos sobre su relación con los mecanismos moleculares fundamentales subyacentes implicados, siguen siendo limitados. MÉTODO: En este estudio, 40 ratas machos SpragueDawley fueron por igual asignadas de manera aleatoria a un grupo salino y un grupo de morfina. Ambos grupos recibieron entrenamiento de autoadministración de drogas, después de lo cual se establecieron modelos de extinción de manera natural. A su vez, los grupos fueron luego subdivididos en dos subgrupos para realizar pruebas de extinción y recaída. Se procedió a medir las masas cerebrales del núcleo accumbens para la extracción total de proteína. Se realizó una electroforesis bidimensional para determinar manchas proteicas diferenciales. Estas proteínas diferenciales fueron entonces sometidas a enzimólisis e identificadas mediante espectrografía de masa. RESULTADOS: Las proteínas fueron clasificadas como proteína de unión a ácidos grasos, isoforma beta de la subunidad catalítica serinatreonina proteína fosfatasa 2A, isoforma alfa de la subunidad catalítica serinatreonina proteína fosfatasa 2A, subunidad gamma subunidad B" de la serinatreonina proteína fosfatasa 2A, o la proteína CDC37 cochaperona 90 de choque térmico. CONCLUSIÓN: Se detectaron cambios significativos en cinco proteínas entre la extinción y la recaída. Estas proteínas están correlacionadas con la fosforilación y el ciclo del ácido tricarboxílico.

A criança que não dorme: aspectos comportamentais da insônia infantil / The child that does not sleep: behavioral aspects of childhood insomnia

A insônia comportamental é um problema frequente em crianças. Quando não tratada, pode resultar em prejuízos no comportamento, aprendizagem e regulação emocional. O presente artigo aborda a importância da avaliação diagnóstica comportamental em crianças com problemas relacionados ao momento de dormir e aos despertares noturnos. A partir de uma análise funcional detalhada é possível identificar o que mantém os comportamentos inadequados da criança em relação ao sono, e assim traçar um plano de intervenção eficaz. As estratégias comumente usadas para o tratamento da insônia infantil são a extinção e o reforço positivo, consideradas pela literatura como métodos eficazes tanto para a redução de problemas no momento de dormir como para os despertares noturnos.

Pharmacological intervention of conditioned fear and its extinction / 中南大学学报(医学版)

Conditioned fear and its abnormal extinction are involved in the psychopathology of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive enhancing agents have been demonstrated to alter fear extinction in many animal research literatures. The present review has examined the pharmacological role of gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic and neurotrophic mechanism in fear extinction, highlighting great hope for the future treatment of anxiety disorders with new agents based on the fear extinction.

Changes of protein kinase A expressions in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore neurobiological mechanisms of the withdrawal-induced aversion. The changes of protein kinase A were measured in central amygdaloid nucleic (CeA) of conditioned place aversion (CPA) model rats.</p><p><b>METHODS</b>(1) All 72 male SD rats were divided into three groups, model group (MN group), and control group (MS group and SN group). MN group was injected with morphine,6.5 days, 10 mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion training, to develop the CPA model. The MS group was administrated equivalent volume of morphine and saline. Also the SN group was injected with equivalent volume of saline and naloxone. (2) During the process of morphine-induced CPA, the expression of protein kinase A was assayed with immunohistochemistry in the CeA.</p><p><b>RESULTS</b>In the MN group, protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA (P < 0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P < 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA expressions were not significantly different both in MS group (P > 0.05)and SN group (P > 0.05).</p><p><b>CONCLUSION</b>(1) Protein kinase A expression, in turn regulating the aversion expression, in the CeA probably is a key pathway contributing to the development of CPA. (2) The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.</p>

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.

Asociaciones excitatorias entre el contexto y la consecuencia en la reinstalación de respuestas extinguidas en el aprendizaje causal humano / Excitatory context-consequence associations in the reinstatement of extinguished responses in human causal learning

En dos experimentos, estudiantes universitarios aprendieron una relación predictiva entre un evento y una consecuencia, la que posteriormente fue extinguida presentando el evento sin la consecuencia. En el Experimento 1, se presentó la consecuencia por sí sola después de la extinción, ocasionando la reaparición de la relación predictiva aprendida originalmente, asemejándose al fenómeno del condicionamiento Pavloviano conocido como "reinstalación". Este experimento demostró además, que no es necesario apelar a asociaciones inhibitorias para explicar la reinstalación, sino que solamente a asociaciones excitatorias entre el contexto y la consecuencia. El Experimento 2 confirmó la generalidad de estos hallazgos utilizando otro procedimiento de aprendizaje causal. Se discuten estos hallazgos en términos de las diferencias entre el aprendizaje causal y el condicionamiento Pavloviano y de la posible existencia de dos mecanismos alternativos de extinción: desaprendizaje para extinguir asociaciones no consolidadas e inhibición para las consolidadas.

In two experiments, undergraduates learned a predictive relationship between an event and a consequence, which was subsequently extinguished by presenting the event without the consequence. In Experiment 1, participants were exposed to the consequence by itself after extinction, occasioning the reappearance of the originally learned predictive relationship, resembling a phenomenon known as Reinstatement in the field of Pavlovian conditioning. This experiment further demonstrated that reinstatement can be explained without appealing to inhibitory associations, but only by mean of excitatory associations between the context and the consequence. Experiment 2 confirmed the generality of these findings using a different procedure of causal learning. The findings are discussed in terms of differences between Pavlovian conditioning and causal learning and of the possible existence of two mechanisms of extinction: unlearning to extinguish non consolidated associations and inhibition for the consolidated associations.

Modulación contextual de la tolerancia asociativa al etanol / Ocassion setting of associative tolerance to ethanol

Existe evidencia que señala que las claves pareadas con drogas no sólo son asociadas con los efectos de éstas, sino que también adquieren propiedades modulatorias de la asociación entre otras claves y los efectos de la droga, contribuyendo así al desarrollo de la tolerancia asociativa (Ramos, Siegel & Bueno, 2002). Utilizando un procedimiento de discriminación derasgo positivo, en la presente investigación evaluamos la contribución de los contextos como moduladores del efecto atáxico del etanol en ratas. Los resultados sugieren que el contexto adquiere propiedades modulatorias de la tolerancia a las drogas y que estas propiedades puedenser extinguidas.

There is evidence that drug-paired cues not only become associated with the drug effects but also become occasion setters that modulate the association of other cues with the drug effects,contributing to the development of associative tolerance (Ramos, Siegel, & Bueno, 2002). Using a feature-positive discrimination training, we evaluated the contribution of contexts asoccasion setters of the ataxic effect of ethanol in rats. The results suggest that the context acquire occasion setter properties of the drug tolerance, and that these properties can be extinguished.

[ role of intrahippocampal microinjections of anisomycin on dexamethasone-induced modulation of memory consolidation in rats]

Evidence indicates that hippocampus and activation of glucocorticoid receptors in this area are necessary for emotional learning and memory processes; also some studies suggest that glucocorticoid's effects probably involve with processes of protein synthysis in the hippocmapus. The aim of this study was to determine the role of intrahippocampal microinjections of anisomycin [[AIMS] as a protein synthysis inhibitor]] on dexamethasone-induced modulation of memory consolidation in the passive avoidance learning [PAL] task in rats. In this study, 90 male Wistar rats [250-300 gr] were surgically implanted bilaterally with cannulae aimed at the dorsal hippocampus [DH] were trained in PAL task. In experiment 1. Dexamethasone [0.1, 0.5, 1 and 3 mg/kg IP] was injected immediately after training and vehicle injected into DH. In experiment 2. Anisomycin [0.5,1 micro g/ micro l/side] or vehicle were injected bilaterally into the DH followed immediately by IP injection of Dexamethasone [1 mg/kg] or vehicle. Two days after training, retention tests were done and step-through latency [STL] and total time spent in light chamber [TLC] of apparatus were recorded during 10 min and compared with controls. Data indicated that injection of Dexamethasone immediatly after training enhanced memory consolidation [P<0.01] and this effect was blocked by injection of ANS in to the DH [P<0.01]. The findings above showed that glucocorticoids play on important role in consolidation of emotional learning and probably in processes of protein synthesis in the hippocampus may play an important role in mediating these effects

The extinction of conditioned fear: structural and molecular basis and therapeutic use

OBJECTIVE: Through association, a large variety of stimuli acquire the property of signaling pleasant or aversive events. Pictures of a wedding or of a plane disaster may serve as cues to recall these events and/or others of a similar nature or emotional tone. Presentation of the cues unassociated with the events, particularly if repeated, reduces the tendency to retrieve the original learning based on that association. This attenuation of the expression of a learned response was discovered by Pavlov 100 years ago, who called it extinction. In this article we review some of the most recent findings about the behavioral and biochemical properties of extinction. RESULTS AND DISCUSSION: It has been shown that extinction is a new learning based on a new link formed by the cues and the absence of the original event(s) which originated the first association. Extinction does not consist of the erasure of the original memory, but of an inhibition of its retrieval: the original response reappears readily if the former association is reiterated, or if enough time is allowed to pass (spontaneous recovery). Extinction requires neural activity, signaling pathways, gene expression and protein synthesis in the ventromedial prefrontal cortex and/or basolateral amygdala, hippocampus, entorhinal cortex and eventually other areas. The site or sites of extinction vary with the task. CONCLUSIONS: Extinction was advocated by Freud in the 1920's for the treatment of phobias, and is used in cognitive therapy to treat diseases that rely on conditioned fear (phobias, panic, and particularly posttraumatic stress disorder). The treatment of learned fear disorders with medications is still unsatisfactory although some have been shown useful when used as adjuncts to behavioral therapy.

OBJETIVO: Muitos estímulos podem adquirir características prazerosas ou aversivas por meio da formação de associações. Fotografias de um casamento ou de um acidente aeronáutico podem servir como dicas para lembrar esses eventos e outros de natureza ou caráter emocional semelhante. Porém, sabe-se que a apresentação repetida de uma dica na ausência do estímulo ao qual está associada reduz a probabilidade de expressão da memória em questão. Este fenômeno de atenuação foi descoberto por Pavlov há quase 100 anos, recebendo o nome de extinção. Neste artigo de revisão, comentamos alguns dos achados mais recentes a respeito das propriedades comportamentais e bioquímicas do processo de extinção de memórias. RESULTADOS E DISCUSSÃO: Tem sido demonstrado que a extinção não envolve esquecimento, mas a inibição da expressão da memória original juntamente com um novo aprendizado, que inclui a formação de uma relação entre a dica e a ausência do estímulo que originou a primeira associação. De fato, a memória original reaparece rapidamente após a re-exposição ao estímulo adequado ou, simplesmente, com o passar do tempo (recuperação espontânea). A extinção requer atividade neural, diferente vias de sinalização neuronal, incluindo a expressão de genes e a síntese de proteínas, em diferentes áreas do cérebro. Estas variam com a tarefa, mas distintos estudos sugerem que tanto o córtex pré-frontal medial como o córtex entorrinal, a amígdala basolateral, hipocampo entre outras áreas desempenham um papel fundamental neste processo. CONCLUSÕES: Nos anos 20 do século XX, Freud recomendou a utilização de terapias baseadas na extinção para o tratamento de fobias. Hoje, a extinção é utilizada na terapia cognitiva de distintas desordens, incluindo o pânico e o estresse pós-traumático. Ainda que alguns medicamentos tenham demonstrado sua eficácia como coadjuvantes na terapia comportamental do medo aprendido, a resposta destes pacientes ao tratamento farmacológico ainda...

Stimulus specificity in the acquisition and extinction of conditioned taste aversion

An experiment evaluated whether the acquisition and extinction of conditioned taste aversion in the rat is stimulus-specific by testing the degree of response transfer between sweet and salty tastes. Animals in the paired-same and paired-different groups received a presentation of a gustatory CS and a cyclophosphamide injection US. Nonconditioned control groups received unpaired CS /US presentations or the CS followed by a vehicle injection. Taste avoidance was evaluated in three nonreinforced test sessions. In the paired-same, unpaired and vehicle groups, all test sessions were conducted with the same flavor as originally used in training, whereas the paired-different group was tested with a novel flavor on the first and second sessions and with the originally trained flavor in last session. Stimulus specific acquisition was apparent in the first test session, when the animals in the group paired-same exhibited lower fluid intake than the other three groups. Evidence of specificity of extinction was apparent in the last test session, when animals in the group paired-different exhibited lower fluid intake than the other three groups. These results provide further evidence of stimulus specificity in acquisition and extinction of conditioned taste aversion, supporting the associative interpretation of these phenomena.

O papel da memória no medo adquirido / The paper of the memory in the acquired fear

Esta revisão procura descrever os aspectos peculiares à memória e sua função tanto na formação do medo adquirido quanto no seu tratamento. busca-se explicar quais mecanismos bioquímicos e funcionais sobre a memória, o esquecimento, a extinção e sobre a repressão da sua formação. foi utilizada bibliografia atual de periódicos indexados a respeito de estudos tanto em animais experimentais quanto em seres humanos, assim como clássicos históricos da literatura científica mundial.

Fundamentos de las terapias de exposición contra las fobias: una propuesta teórica integradora de la conducta de evitación / Principles of exposition therapy against phobias: an integrative theoretical model of avoidance behavior

Se presenta una teoría de la conducta de evitación basada en la integración de procesos de aprendizaje y motivación, con el fin de poder predecir los resultados de los procedimientos terapéuticos contra las fobias, basados en el principio de exposición. Antes de introducir la propuesta teórica, se ofrecen algunas generalidades sobre las fobias y sus componentes conductuales: la evitación y el escape. A continuación, se presentan las principales teorías sobre la adquisición y la extinción de la conducta de evitación. Luego se explican las terapias de exposición con base en la extinción de la conducta de evitación. Finalmente, se introduce el modelo teórico, que hace una mejor predicción de los resultados de las terapias de exposición, con respecto a las teorías tradicionales, las cuales se basan exclusivamente en principios de aprendizaje.