Expressão de zif-268 durante a aquisição, evocação e extinção de uma memória aversiva

In the behavioral paradigm of discriminative avoidance task, both short and long-term memories have been extensively investigated with behavioral and pharmacological approaches. The aim of the present study was to evaluate, using the abovementioned model, the hippocampal expression of zif-268 - a calcium-dependent immediate early gene involved with synaptic plasticity process - throughout several steps of memory formation, such as acquisition, evocation and extiction. The behavioral apparatus consisted of a modified elevaated plus-maze, with their enclosed arms disposed in "L". A pre-exposure to the maze was made with the animal using all arms enclosed, for 30 minutes, followed by training and test, during 10 minutes each. The between sections interval was 24h. During training, aversive stimuli (bright light and loud noise) were actived whenever the animals entered one of the enclosed armas (aversive arm). Memory acquisiton, retention and extinction were evaluated by the percentage of the total time spent exploring the aversive arm. The parameters evaluated (time spent in the arms and total distance traveled) were estimated with an animal tracking software (Anymaze, Stoelting, USA). Learning during training was estimated by the decrease of the time spent exploring the aversive arm. One hour after the beginning of each section, animals were anaesthetized with sodium-thiopental (i.p.) and perfused with 0.9% heparinized saline solution followed by 4% paraformaldehyde. Brains were cryoprotected with 20% sucrose, separeted in three blocks and frozen. The middle block, containing the hippocampus, was sectioned at 20 micro meters in the coronal plane and the resutant sections were submitted to zif-268 immunohistochemistry. Our results show an increased expression of zif-268 in the dentate gyrus (DG) during the evocation and extinction stages. There is a distinct participation of the DG during the memory evocation, but not during its acquisition. Inaddition, all hippocampal regions (CA1, CA3 and DG) presented an increased zif-268 expression during the process of extinction.

Neurofisiologia hipocampal durante sessões de sono intercaladas por exploração espacial: Reverberação do passado ou predição do futuro?

The ability to predict future rewards or threats is crucial for survival. Recent studies have addressed future event prediction by the hippocampus. Hippocampal neurons exhibit robust selectivity for spatial location. Thus, the activity of hippocampal neurons represents a cognitive map of space during navigation as well as during planning and recall. Spatial selectivity allows the hippocampus to be involved in the formation of spatial and episodic memories, including the sequential ordering of events. On the other hand, the discovery of reverberatory activity in multiple forebrain areas during slow wave and REM sleep underscored the role of sleep on the consolidation of recently acquired memory traces. To this date, there are no studies addressing whether neuronal activity in the hippocampus during sleep can predict regular environmental shifts. The aim of the present study was to investigate the activity of neuronal populations in the hippocampus during sleep sessions intercalated by spatial exploration periods, in which the location of reward changed in a predictable way. To this end, we performed the chronic implantation of 32-channel multielectrode arrays in the CA1 regions of the hippocampus in three male rats of the Wistar strain. In order to activate different neuronal subgroups at each cycle of the task, we exposed the animals to four spatial exploration sessions in a 4-arm elevated maze in which reward was delivered in a single arm per session. Reward location changed regularly at every session in a clockwise manner, traversing all the arms at the end of the daily recordings. Animals were recorded from 2-12 consecutive days. During spatial exploration of the 4-arm elevated maze, 67,5% of the recorded neurons showed firing rate differences across the maze arms. Furthermore, an average of 42% of the neurons showed increased correlation (R>0.3) between neuronal pairs in each arm. This allowed us to sort representative neuronal subgroups for each maze arm, and to analyze the activity of these subgroups across sleep sessions. We found that neuronal subgroups sorted by firing rate differences during spatial exploration sustained these differences across sleep sessions. This was not the case with neuronal subgroups sorted according to synchrony (correlation). In addition, the correlation levels between sleep sessions and waking patterns sampled in each arm were larger for the entire population of neurons than for the rate or synchrony subgroups. Neuronal activity during sleep of the entire neuronal population or subgroups did not show different correlations among the four arm mazes. On the other hand, we verified that neuronal activity during pre-exploration sleep sessions was significantly more similar to the activity patterns of the target arm than neuronal activity during pre-exploration sleep sessions. In other words, neuronal activity during sleep that precedes the task reflects more strongly the location of reward than neuronal activity during sleep that follows the task. Our results suggest that neuronal activity during sleep can predict regular environmental changes

Sonhos antecipatórios: influência de um evento significativo da vigília na atividade onírica

In most cultures, dreams are believed to predict the future on occasion. Several neurophysiological studies indicate that the function of sleep and dreams is to consolidate and transform memories, in a cyclical process of creation, selection and generalization of conjectures about the reality. The aim of the research presented here was to investigate the possible adaptative role of anticipatory dreams. We sought to determine the relationship between dream and waking in a context in which the adaptive success of the individual was really at risk, in order to mobilize more strongly the oneiric activity. We used the entrance examination of the Federal University of Rio Grande do Norte (UFRN) as a significant waking event in which performance could be independently quantified. Through a partnership with UFRN, we contacted by e-mail 3000 candidates to the 2009 examination. In addition, 150 candidates were approached personally. Candidates who agreed to participate in the study (n = 94) completed questionnaires specific to the examination and were asked to describe their dreams during the examinaton period. The examination performance of each candidate in the entrance examination was provided by the UFRN to the researcher. A total of 45 participants reported dreams related to the examination. Our results show a positive correlation between performance on the examination and anticipatory dreams with the event, both in the comparison of performance on objective and discursive, and in final approval (in the group that not dreamed with the exam the rate of general approval, 22,45%, was similar to that found in the selection process as a whole, 22.19%, while for the group that dreamed with the examination that rate was 35.56%). The occurrence of anticipatory dreams reflectes increased concern during waking (psychobiological mobilization) related to the future event, as indicated by higher scores of fear and apprehension, and major changes in daily life, in patterns of mood and sleep, in the group that reported testrelated dreams. Furthermore, the data suggest a role of dreams in the determination of environmentally relevant behavior of the vigil, simulating possible scenarios of success (dream with approval) and failure (nightmares) to maximize the adaptive success of the individual

Antidepressivos modificam a extinção de uma memória aversiva em ratas

Treatment of major depression, posttraumatic stress disorder and other psychopathologies with antidepressants can be associated with improvement of the cognitive deficits related to these disorders. Although the mechanisms of these effects are not completely elucidated, alterations in extinction of aversive memories are believed to be present in these psychopathologies. Moreover, researches with laboratory animals usually focus on male subjects, and we have recently verified that extinction of an aversive task is reduced in female rats when compared to males. In the present study, female rats were long-term treated with clinically used antidepressants (fluoxetine, nortriptyline or mirtazapine) and tested in the plus-maze discriminative avoidance and forced swimming tests in order to evaluate learning, memory, extinction, anxiety and depression-related behaviors. All groups learned the task, but learning was somewhat faster in nortriptyline and mirtazapine-treated animals . Task retrieval was also showed by all experimental groups. Chronic treatment with fluoxetine, but not with the other antidepressants, increased extinction of the discriminative task. In the forced swimming test, animals treated with fluoxetine and mirtazapine showed decreased immobility duration. In conclusion, antidepressants interfere with learning and female rats treated with fluoxetine presented increased extinction of the aversive memory task. On the other hand, both fluoxetine and mirtazapine were effective in the forced swimming test, suggesting dissociation between the antidepressant effects and the extinction of aversive memories

Influência do ciclo estral no efeito do diazepam na ansiedade e memória de ratas

Memory and anxiety are related phenomena. Several evidences suggest that anxiety is fundamental for learnining and may facilitate or impair the memory formation process depending of the context. The majority of animal studies of anxiety and fear use only males as experimental subjects, while studies with females are rare in the literature. However, the prevalence in phobic and anxiety disorders is greater in women than in men. Moreover, it is known that gender maybe influence benzodiazepine effects, the classic drugs used for anxiety disorders treatment. In this respect, to further investigate if fear/anxiety aspects related to learning in female subjects would contribute to the study of phobic and anxiety disorders and their relationship with learning/memory processes, the present work investigates (a) the effects of benzodiazepine diazepam on female rats performance in a aversive memory task that assess concomitantly anxiety/emotionality, as the interaction between both; (b) the influence of estrous cycle phases of female rats on diazepam effects at aversive memory and anxiety/emotionality, and the interaction between both and (c) the role of hormonal fluctuations during estrous cycle phases in absence of diazepam effects in proestrus, because female rats in this phase received or not mifepristone, the antagonist of progesterone receptor, previously to the diazepam treatment. For this purpose, the plus maze discriminative avoidance task, previously validated for studies of anxiety concomitantly to learning/memory, was used. The apparatus employed is an adaptation of a conventional plus maze, with two opens arms and two closed arms, one of which presenting aversive stimulation (noise and light). The parameters used were: time in non-aversive arm compared to time in aversive and percentage of time in aversive arm on several temporal divisions, in order to evaluate memory; percentage of time in open arms, risk assessment, head dipping and end exploring to evaluate anxiety ; and distance traveled for locomotion. In experiment I, we found anxiolytic effect of diazepam only for 4 mg/kg dose, however the amnestic effect appear at a dose of 2 mg/kg. In second experiment, rats were divided in groups according estrous cycle phase (metaestrus/diestrus, proestrus e estrus). In this experiment, when we considered estrous cycle phase or diazepam treatment, the results did not demonstrate any differences in anxiety/emotionality parameters. The amnestic effects of diazepam occur in female rats in metestrus/diestrus and estrus and is absent in proestrous rats. Proestrous female rats that received mifepristone exhibited the amnestic effect of diazepam and also anxiolytic effects, that it was not previously observed in this dose. The results have demonstrated dissociation of anxiolytic and amnestic diazepam effects, not previously observed in males; the absence of amnestic effect of diazepam in proestrous phase; and the possible role of progesterone in aversive memory over diazepam effect, because the mifepristone, associated with diazepam, caused amnestic effect in proestrus

Alterações do ciclo sono-vigília moduladas por Dopamina e suas consequências Mnemônicas

Neuroscience is on a rise of discoveries. Its wide interdisciplinary approach facilitates a more complex understanding of the brain, covering various areas in depth. However, many phenomena that fascinate human kind are far from being fully elucidated, such as the formation of memories and sleep. In this study we investigated the role of the dopaminergic system in the process of memory consolidation and modulation of the phases of sleep-wake cycle. We used two groups of animals: wildtype mice and hiperdopaminergic mice, heterozygous for the gene encoding the dopamine transporter protein. We observed in wild-type mice that the partial blockade of the D2 dopamine receptor by the drug haloperidol caused deficits in memory consolidation for object recognition, as well as a significant reduction in the duration of rapid eye movement sleep (REM). We also found a mnemonic deficit without pharmacological intervention in hiperdopaminergic animals; this deficit was reversed with haloperidol. The results suggest that dopamine plays a key role in memory consolidation for object recognition. The data also support a functional relationship between the dopaminergic system and the modulation of REM sleep

Alterações na evocação de uma memória aversiva ao liongo do ciclo estral de ratas: influências da transmissão gabaérgica na amígdala

GABAergic neurotransmission has been implicated in many aspects of learning and memory, as well as mood and anxiety disorders. The amygdala has been one of the major focuses in this area, given its essential role in modulating emotionally relevant memories. However, studies with male subjects are still predominant in the field. Here we investigated the consequences for an aversive memory of enhancing or decreasing GABAergic transmission in the basolateral nucleus of the amygdala (BLA). Wistar female rats were trained in the plus-maze discriminative avoidance task, in which they had to learn to avoid one of the enclosed arms where an aversive stimulus consisting of a bright light and a loud noise was given (day 1). Fifteen minutes before the test session (day 2) animals received 0,2 μL infusions of either saline solution, the GABAergic agonist muscimol (0,05 mg/ml), or the GABAergic antagonist bicuculine (0,025 mg/ml) bilaterally intra-BLA. On the test day, females in proestrous or estrous presented adequate retrieval and did not extinguish the task, while females in metestrous or diestrous presented impaired retrieval. In the first group, muscimol infusion impaired retrieval and bicuculline had no effect, suggesting naturally low levels of GABAergic transmission in the BLA of proestrous and estrous females. In the second group, muscimol infusion had no effect and bicuculline reversed retrieval impairment, suggesting naturally high levels of GABAergic transmission in the BLA of metestrous and diestous females. Additionally, proestrous and estrous females presented higher anxiety levels compared to metestrous and diestrous females, which could explain better performance of this group. On the other hand, BLA GABAergic system did not interfere with the innate fear response because drug infusions had no effect in anxiety. Thus, retrieval alterations caused by the GABAergic drugs were probably related specifically to memory processes

Investigação da influência do cochilo na aprendizagem escolar

There is a known positive effect of nocturnal sleep for brain plasticity and the consolidation of declarative and procedural memories, as well as for the facilitation of insight in problem solving. However, a possible pro-mnemonic effect of daytime naps after learning is yet to be properly characterized. The goal of this project was to evaluate the influence of daytime naps on learning among elementary and middleschool students, measuring the one-day (acute), and semester-long (chronic) effects of post-learning naps on performance. In the Acute Day-Nap condition, the elementary students were exposed to a class and then randomly divided into three groups: Nap (N), Game-based English Class (GBEC) and Traditional English Class (TEC). There were 2 multiple-choice follow-up tests to evaluate students performance in the short and long runs. In the short run, the N group outperformed the other two groups; and such tendency was maintained in the long run. In the chronic condition, the middle-school students were randomly separated into two groups: Nap (N) and Class (C) and were observed during one academic term. The N group had increased school performance in relation to the C group. In the statistical analyses, independent t-tests were applied considering the scores significant when p<0,05, expressed in terms of average ± average standard error. Results can be interpreted as an indication that a single daytime nap opportunity is not enough to ensure learning benefits. Therefore, more research is needed in order to advocate in favor of a daytime nap as a pedagogical means of promoting enhanced school performance

Efeitos de diferentes tipos estressores sobre a memória e aprendizagem de ratas

The exposure to stressors produces physiological changes of the organism in order to adapt the individual to the environment. Depending on the type, intensity and duration, stress can affect some cognitive functions, particularly processes of learning and memory. Several studies have also proposed that some level of anxiety would be necessary for memory formation. In this context, memories of previously aversive experiences may determine the manner and intensity with which are expressed fear responses, which explains the great interest in analyzing both anxiety and memory in animals. In addition, males and females demonstrate different reactions in relation to stressful stimuli, showing different levels of anxiety and differences in processing of the acquisition, retention and recall of information. Based on this information, the present study aimed to verify the effect of stress on learning, memory and anxiety behavioral parameters in rats exposed at different types of stressors of long duration (seven consecutive days): restraint (4h/day), overcrowding (18h/day) and social isolation (18h/day) in the different phases of the estrous cycle. Our results showed that the stress induced by restraint and social isolation did not cause changes in the acquisition process, but impaired the recall of memory in rats. Furthermore, it is suggested a protective effect of sex hormones on retrieval of aversive memory, since female rats in proestrus or estrus phase, characterized by high estrogen concentrations, showed no aversive memory deficits. Furthermore, despite the increased plasma levels of corticosterone observed in female rats subjected to restraint stress and social isolation, anxiety levels were unaltered, compared to those various stress conditions. Animal models based on psychological and social stress have been extensively discussed in the literature. Correlate behavioral responses, physiological and psychological have contributed in increasing the understanding of stress-induced psychophysiological disorders

Efeito do alerta e valência emocional nos componentes de lembrança e familiaridade da memória episódica

The episodic memory system allows us to retrieve information about events, including its contextual aspects. It has been suggested that episodic memory is composed by two independent components: recollection and familiarity. Recollection is related to the vivid e detailed retrieval of item and contextual information, while familiarity is the capability to recognize items previously seen as familiars. Despite the fact that emotion is one of the most influent process on memory, only a few studies have investigated its effect on recollection and familiarity. Another limitation of studies about the effect of emotion on memory is that the majority of them have not adequately considered the differential effects of arousal and positive/negative valence. The main purpose of the current work is to investigate the independent effect of emotional valence and arousal on recollection and familiarity, as well as to test some hypothesis that have been suggested about the effect of emotion on episodic memory. The participants of the research performed a recognition task for three lists of emotional pictures: high arousal negative, high arousal positive and low arousal positive. At the test session, participants also rated the confidence level of their responses. The confidence ratings were used to plot ROC curves and estimate the contributions of recollection and familiarity of recognition performance. As the main results, we found that negative valence enhanced the component of recollection without any effect on familiarity or recognition accuracy. Arousal did not affect recognition performance or their components, but high arousal was associated with a higher proportion of false memories. This work highlight the importance of to consider both the emotional dimensions and episodic memory components in the study of emotion effect on episodic memory, since they interact in complex and independent way

Investigação da memória autobiográfica em idosos com demência de Alzheimer nas fases leve e moderada

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Cartografia de uma intervenção comunitária para prevenção de DST/HIV/AIDS

Community-based interventions have been presented as a proposal of operationalization of the concept of vulnerability to STD/Aids prevention. This study aimed to analyze the Community intervention developed through the project Strengthening of Community action networks for STD/Aids prevention: know and intervenein, at Mãe Luiza neighborhood, in the city of Natal, State of Rio Grande do Norte, Brazil. The study was conducted in the same location where intervention occurs and took as time reference the first 30 months of construction and deployment process, from April 2010 until December 2012. This is research with qualitative approach, participatory character, developed from the immersion of the researcher in the field, being this community intervention itself. In this perspective, the study approximates to the Cartographic method in which the researcher-researched is engendered in the acts and effects research. The data-generating sources were the memories of the researcher from the field notes, written narratives of subjects involved in the intervention and documents pertaining to the project. In the methodological path of cartography, the image of the rhizome by Deleuze and Guattari (1995) has accompanied the immersion in the field given the nature of research-intervention which approach to the concept of object-Rhizome. The presentation of results was composed for the attempted rhizomatic and a hypertext representation, based on the descriptive narrative taken from the documentary analysis and the multi-faceted narratives with the voices, the looks and the affections narrated by the subject involved, respectively. On the path taken, three lanes were drawn as synthesis of learning produced by experience-that can contribute to understanding the process under study, in his singular character, and reflections on other experiences of community intervention: track 1- Community intervention as active-reflective space and a cause; track 2 Inclusion as power and challenge of community involvement; track 3 Sustainability as A challenge of Community intervention. The study indicates that community intervention is presented as a potential producer of health as also produces practical and creative skills, subjects and inventive in the daily life of the community with a view to reinventing knowledge and practices for the prevention of STD/HIV/Aids

Lembranças de alunos, imagens de professores: narrativas e diálogos sobre a formação médica

Se trata de una incursión histórica por el pensamiento y por la enseñanza médica, discutiéndose la formación médica de manera contextualizada, con el objetivo de comprenderla para interpretarla a través del recuerdo que haya sido fijado por los alumnos. Se dará un enfoque a la mediación pedagógica de esa formación, intentando proporcionar el diálogo entre la historia social de la Medicina y los recuerdos de alumnos, ubicándolas en un contexto histórico-social y cultural, al mismo tiempo en que se ha buscado sujetar las imágenes de los profesores que hayan dejado huellas significativas en la vida de los alumnos, en cuestiones profesionales, sociales y culturales. Se configura, asimismo, una memoria de la formación médica de la Faculdade de Medicina da Universidade Federal do Rio Grande do Norte (UFRN), desde su creación en el 1955, como Faculdade de Medicina de Natal, hasta el 1963, como Faculdade de Medicina da UFRN. Los recuerdos han sido recolectados por medio de entrevistas temáticas con alumnos ya formados de las tres primeras turmas concluyentes, de los años del 1961, 1962 y 1963, de la referida Facultad y fueron interpretadas utilizándose la cartografía como técnica que envuelve la construcción de cuadros interpretativos, teniendo como unidad de análisis las palabras representativas de los elementos constituyentes de la mediación pedagógica, sacadas de las narrativas de los sujetos, que cargan también las imágenes de los profesores que han compuesto dicho diálogo por sus contribuciones para la existencia del saber y hacer de la educación médica en Natal/RN. Aún se comprende que esa Facultad fue creada en un momento histórico-social y cultural en que Brasil y el mundo todavía intentaban encontrar nuevos caminos, después de turbulencias causadas por la Segunda Guerra Mundial, y la intelectualidad natalense visualizaba el encaje de la ciudad en los parámetros de la modernidad. El currículum implantado era técnico/racional, pero al ser interpretado por la acción, a través de la reconstrucción de los recuerdos de los alumnos, en los vestigios de la mediación pedagógica de la formación médica y en las imágenes de los profesores todavía vivas en sus memorias, se vuelve posible entender que a esos alumnos ha sido enseñado: un saber relacional que permitía el diálogo, la transmisión de experiencia y el compromiso médico con vista a un atendimiento a la populación en primer lugar, siguiéndole el sentimiento que fomentaba deseos de ayuda al próximo, siendo los propios profesores el ejemplo, conformándose, así, con un saber contextual, agregado a una participación política y de responsabilidad ética para con la sociedad

Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors

The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

Histerese térmica de sistemas magnéticos nanoestruturados

We report a theoretical investigation of thermal hysteresis in magnetic nanoelements. Thermal hysteresis originates in the existence of meta-stable states in temperature intervals which may be tuned by small values of the external magnetic field, and are controlled by the systems geometric dimensions as well as the composition. Two systems have been investigated. The first system is a trilayer consisting of one antiferromagnetic MnF2 film, exchange coupled with two Fe lms. At low temperatures the ferromagnetic layers are oriented in opposite directions. By heating in the presence of an external magnetic field, the Zeeman energy induces a gradual orientation of the ferromagnets with the external field and the nucleation of spin- op-like states in the antiferromagnetic layer, leading eventually, in temperatures close to the Neel temperature, to full alignment of the ferromagnetic films and the formation of frustrated exchange bonds in the center of the antiferromagnetic layer. By cooling down to low temperatures, the system follows a different sequence of states, due to the anisotropy barriers of both materials. The width of the thermal hysteresis loop depends on the thicknesses of the FM and AFM layers as well as on the strength of the external field. The second system consists in Fe and Permalloy ferromagnetic nanoelements exchange coupled to a NiO uncompensated substrate. In this case the thermal hysteresis originates in the modifications of the intrinsic magnetic