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Prejuízo de memória do tipo episódica induzido pela Cetamina: diferenças funcionais na expressão de c-Fos em sub-regiões do hipocampoSouza, Ingrid Brasilino Montenegro Bento de 24 April 2015 (has links)
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Previous issue date: 2015-04-24 / Episodic-like memory is a subtype of declarative memory that refers recall an integration of where and when a certain event (what) happened. The hippocampus –subregions function in pattern separation process are key to mediating of episodic memory recall. Glutamatergic neurotransmission, particularly AMPA and NMDA receptors, have been characterized as essential in neuroplastic processes. Ketamine is a non-competitive NMDA antagonist available at clinical practice with effect on cognitive performance and plasticity. This study’s goal was to evaluate the acute action of ketamine on behavioral and neurochemical aspects of episodic-like memory through immediate-early gene expression (IEG), c-Fos. The experimental procedure was done at a circular arena, and consists of two training sessions and a test of five minutes each. In the first training, the animal was placed in a circular open field to explore four similar objects (A), after a 1 hour, the rats start a second sample with four other objects (B), two of those appear in different spatial locations relative for the first sample. In the test, four objects are shown, two recent-familiar (B) and two old-familiar (A), two displaced (A2, B2) and two stationary (A1 and B1). Forty-six 3-month-old male Wistar rats were separated in five groups. The home cage group (n=6; without apparatus exposure) was used to measure IEG basal expression. The other four groups, with 10 rats each, went through the behavioral test. One of them received saline 0.9% and the other two received 8 mg/kg or 15 mg/kg ketamine ip immediately after the second sample, while the control group received no treatment. All objects and spatial location in this protocol were randomized among groups. The analyses were blinded for groups and the behavioral measures were distance, speed and time of exploration in all sessions. The exploration ratio and discrimination ratio of the four objects in the test session were calculated. Wilcoxon test showed statistically significant differences between these pairs of objects in the control group: A1> A2, B2> B1 and A1> B1. The data indicate that these rats could integrate the three elements of episodic-like memory. The saline group demonstrated the same exploration pattern of control group for comparisons between A1>A2 and B2>B1, but statistical differences were not found between A1and B1. The Welch’s analysis showed a difference of c-Fos expression in all hippocampal sub-regions. The control group had the highest c-Fos expression in the dentate gyrus when compared to the other groups, suggesting the role of this sub-region for integration of episodic-like memory. The two sub-anesthetic doses of ketamine induced a deficit for this type of memory. The highest dose demonstrated a possible hypolocomotion effect, characterized by decreasing of total distance traveled and speed, compared to the other groups at the test session. In short, the deficit of episodic-like memory was characterized both as amnesic effect of ketamine and as decrease of c-Fos in the dentate gyrus of those groups, suggesting a possible role of this field in episodic-like memory formation. / A memória similar à episódica é um subtipo de memória declarativa que se refere à recordação, de forma integrada, de onde e quando um determinado evento (o quê) aconteceu. A funcionalidade das sub-regiões do hipocampo dorsal no processo de separação de padrões apresenta-se como mediadora chave da recordação episódica. A neurotransmissão glutamatérgica, em especial dos receptores AMPA e NMDA, caracteriza-se como essencial em processos neuroplásticos. A Cetamina é um dos poucos antagonistas não competitivos NMDA disponíveis na prática clínica com efeitos no desempenho cognitivo e na plasticidade. O objetivo do presente estudo foi avaliar a ação aguda da Cetamina no comportamento da memória do tipo episódica e a funcionalidade das sub-regiões hipocampais (CA1, CA3 (ab e c) e GD), através da expressão do gene imediato (IEG), c-Fos. O procedimento experimental, realizado em uma arena circular, consistiu em duas sessões de treino e uma de teste com duração de cinco minutos cada. No primeiro treino, o animal é colocado em um campo aberto circular para explorar quatro objetos iguais (A), após o intervalo de 1 hora, o rato inicia o segundo treino com outros quatro objetos (B), destes dois aparecem em disposições espaciais não alocadas na primeira sessão. Na etapa do teste são apresentados quatro objetos, sendo dois recentes (B) e dois antigos (A), dois deslocados (A2 e B2) e dois estacionários (A1 e B1). Neste estudo, 46 ratos Wistar machos adultos foram divididos em cinco grupos. O grupo home cage foi escolhido como controle para a avaliação basal dos IEGs nas sub-regiões do hipocampo dorsal. Quatro grupos, contendo 10 animais cada, realizaram o procedimento comportamental, sendo um grupo controle e três grupos que passaram por intervenção farmacológica: um grupo que recebeu Salina 0.9% (i.p.) e os outros dois receberam a Cetamina (i.p.), nas doses de 8mg/kg e 15 mg/kg, imediatamente após o segundo treino. As análises do estudo foram duplo-cego e os objetos e suas localizações espaciais foram randomizadas entre os grupos. As medidas comportamentais utilizadas foram a “distância total percorrida”, a “velocidade” e o “tempo de exploração” para todas as sessões. Na sessão de teste também foram calculadas a “taxa de exploração” e a “taxa de discriminação” dos objetos. No teste de Wilcoxon o grupo controle apresentou o desempenho padrão estatisticamente significativo: A1>A2, B2>B1 e A1>B1. Integrando os três elementos da memória episódica, seguido pelo grupo salina que apresentou o mesmo perfil de exploração entre os objetos antigos e recentes, A1>A2, B2>B1. A análise do Welch mostrou diferenças neuroquímicas em todas as sub-regiões do hipocampo, destacando um aumento de c-Fos no giro denteado (GD) dos animais controles quando comparado aos outros grupos, sugerindo o papel desta sub-região para a integração da memória tipo episódica. As duas doses sub-anestésicas da Cetamina induziram um déficit para este tipo de memória. A dose mais elevada demonstrou um possível efeito hipolocomotor, caracterizado pela redução na distância total percorrida e na velocidade, em comparação com os outros grupos, na sessão de teste. Em suma, o déficit de memória tipo episódica foi caracterizado tanto pelo efeito amnésico de Cetamina quanto pela redução de c-Fos no GD desses grupos, sugerindo um possível papel deste campo na formação desse tipo de memória.
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A Comparative Assessment of How Rhesus Monkeys and 3- to 4-year-old Children Remember Self-Agency with Spatial, Temporal, and Contextual Features in Working MemoryHoffman, Megan L 17 August 2012 (has links)
Comparative research on event memory has typically focused on the binding of spatial and temporal information in memory, but much less is known about how animals remember information about the source of their memories (i.e., whether the event is something they performed themselves or whether they observed it). The purpose of the present study was to examine how rhesus monkeys (n = 8) and 3- to 4- year-old children (n = 20) remember this information along with other relevant event features (object identity, spatial location, temporal properties and contextual features) in working memory. In Experiment 1, rhesus monkeys completed five different delayed matching-to-sample tasks to assess independent encoding of these five event components. In Experiment 2, the monkeys either performed or observed an event and then had to respond to a randomly selected pair of memory tests used in the previous experiment. In Experiment 3, children were presented with the same memory task, but were given a brief demonstration to learn how to perform the task. Both children and monkeys responded to these tests using photos and shapes (for the identity and spatial tests) and icons (for the temporal, agency and context tests). The monkeys demonstrated significantly above-chance performance on the identity, spatial, temporal and agency tasks. The children were above chance on the one component the monkeys had difficulty with (context), but conversely demonstrated difficulty on the temporal memory test. There was evidence of feature integration in both monkeys and children. Specifically, the children were significantly more likely to respond correctly to the second memory test if they had also been correct on the first memory test. Two of five rhesus monkeys also showed this effect, indicating that for these individuals, the features were integrated in working memory. Implications of this research are discussed in relation to self-awareness and episodic memory research in children and nonhuman species.
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A Comparative Assessment of How Rhesus Monkeys and 3- to 4-year-old Children Remember Self-Agency with Spatial, Temporal, and Contextual Features in Working MemoryHoffman, Megan L 17 August 2012 (has links)
Comparative research on event memory has typically focused on the binding of spatial and temporal information in memory, but much less is known about how animals remember information about the source of their memories (i.e., whether the event is something they performed themselves or whether they observed it). The purpose of the present study was to examine how rhesus monkeys (n = 8) and 3- to 4- year-old children (n = 20) remember this information along with other relevant event features (object identity, spatial location, temporal properties and contextual features) in working memory. In Experiment 1, rhesus monkeys completed five different delayed matching-to-sample tasks to assess independent encoding of these five event components. In Experiment 2, the monkeys either performed or observed an event and then had to respond to a randomly selected pair of memory tests used in the previous experiment. In Experiment 3, children were presented with the same memory task, but were given a brief demonstration to learn how to perform the task. Both children and monkeys responded to these tests using photos and shapes (for the identity and spatial tests) and icons (for the temporal, agency and context tests). The monkeys demonstrated significantly above-chance performance on the identity, spatial, temporal and agency tasks. The children were above chance on the one component the monkeys had difficulty with (context), but conversely demonstrated difficulty on the temporal memory test. There was evidence of feature integration in both monkeys and children. Specifically, the children were significantly more likely to respond correctly to the second memory test if they had also been correct on the first memory test. Two of five rhesus monkeys also showed this effect, indicating that for these individuals, the features were integrated in working memory. Implications of this research are discussed in relation to self-awareness and episodic memory research in children and nonhuman species.
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A área hipocampal CA1 é essencial para a memória similar à episódicaBarreto, Davi Drieskens Carvalho de Castro Sá 31 March 2016 (has links)
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Previous issue date: 2016-03-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Episodic memory is a declarative type of memory rich in temporal and spatial contexts. This type of memory has been atributed only to humans, but animals have been demonstrating an episodic-like memory, based on behavioural criteria and, considered as a memory for a particular event (“what”) that happened in a particular place (“where”) and in a particular time (“when”). To be considered as an episodic-like memory, these behavioural aspects must be evoked in an integrative and associative way, excluding any possibility of being evoked separately. For a long time it has been demonstrated that the medial temporal lobe (MTL) is important for processes involving episodic-like memory characteristics and, the hippocampus and other areas, such as the perirhinal, postrhinal, entorhinal and medial prefrontal cortices seem to be involved in one or more of episodic-like memory behavioural aspects. In this work we sought to investigate the role of the hippocampal subfield CA1 with bilateral infusions of the GABAA agonist muscimol, in an integrative episodic-like memory task. 24 naïve male wistar rats, ranging from 3 to 4 months, weighing 270-360g and kept in controlled coditions, were used as subjects. This task is done in an open-field and it depends on the tendency of rats to explore novelty. There were three trials: sample 1, sample 2 and test. Each one had a duration of five minutes and the intertrial interval was of 1 hour. In sample 1, rats were allowed to explore four novel objects (A) in specific locations. In sample 2, four new objects (B) were disposed in the open-field, where two of them were placed in locations previously occupied by objects “A”, and two of them were placed in new positions. In the test trial, animals were exposed to four copies of previously seen objects, where two of them were stationary to its initial position (A1 and B1) and another two were displaced (A2 and B2). The pattern of exploration expected to this task is of A1>B1 (temporal pattern), B2>B1 (spatial pattern) and A1>A2 (integrative pattern). Animals of the control group did evoked an episodic-like memory in the test trial, while the animals in the experimental group didn’t. This was not influenced by a lack of exploration in the muscimol group. Histology showed that the cannulae and niddle tips were placed in the right positions. Altogether, our data provides evidence that CA1 plays an essential role in the recollection of the episodic-like memory components, although it’s not clear if it does by having a role in the recognition of objects alone, or on the association of temporal and spatial aspects of episodic-like memory. / A memória episódica é uma memória declarativa rica em contexto espacial e temporal. Este tipo de memória tem sido atribuído apenas a humanos, mas alguns animais têm demonstrado uma memória similar à episódica, baseada em critérios que podem ser mostrados através do comportamento e, tida como a memória para eventos (“o quê”) que ocorreram em um devido local (“onde”) e num determinado espaço de tempo (“quando”). Para ser considerada uma memória similar à episódica, estes aspectos comportamentais devem ser evocados de forma integrada e associativa, não havendo a possibilidade de se recordar cada aspecto separado. Há algum tempo tem sido demonstrado que o lobo temporal medial (LTM) é importante para processos que envolvem características da memória similar à episódica e, o hipocampo e áreas como os córtices perirrinal, pósrrinal, entorrinal e pré-frontal medial parecem estar envolvidas em um ou mais dos aspectos comportamentais deste tipo de memória. Neste trabalho nós procuramos avaliar o papel da área hipocampal CA1 em uma tarefa de memória similar à episódica integrativa dos três aspectos comportamentais através da inativação bilateral com o agonista GABAA muscimol. Para tal, utilizamos 24 ratos wistar machos de 3 a 4 meses de idade, pesando entre 270-360g e mantidos em condições controladas. Esta tarefa é realizada em uma arena circular e é baseada no paradigma da novidade, que aponta que em estado saudável, ratos sempre vão preferir explorar algo novo. Foram realizadas três sessões na tarefa: a sessão de amostra 1, amostra 2 e teste. Cada sessão teve duração de cinco minutos e o intervalo entre sessões foi de uma hora. Na sessão de amostra 1 foi permitido que o animal explorasse quatro objetos novos (A) em disposições específicas. Na sessão de amostra 2 quatro novos objetos (B) foram expostos, sendo dois alocados em posições ocupadas pelos objetos “A” e dois em novas posições. Na sessão de teste os animais entraram em contato dois objetos da primeira sessão e, dois objetos da segunda sessão, onde um objeto de cada sessão era estacionário em relação à sua posição inicial (A1 e B1) e outro objeto era deslocado (A2 e B2). O padrão de exploração esperado para esta tarefa é de A1>B1 (padrão temporal), B2>B1 (padrão espacial) e A1>A2 (padrão integrativo). Os animais do grupo controle conseguiram evocar o episódio na sessão de teste da tarefa, enquanto que os animais do grupo experimental não conseguiram e, isto não foi influenciado por uma falta de motivação em explorar por parte do grupo experimental. Um exame histológico verificou a posição correta das cânulas e agulhas de infusão para a área CA1. Concluímos que CA1 é importante para a resolução da tarefa, mas não fica claro se o é por influenciar no reconhecimento de objetos, ou porque influenciou diretamente no processamento dos aspectos espacial e temporal.
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Změny paměti epizodického typu v průběhu stárnutí / Episodic-like memory changes during agingČechová, Kateřina January 2016 (has links)
The Diploma thesis is concerned with the human episodic-like memory and its changes during the course of healthy ageing. Episodic memory represents a memory of specific events and their spatiotemporal relations, involving conscious retrieval and mental time travel. As a testable analogy in animals, a concept of episodic-like memory has been suggested and defined as a memory of spatiotemporal location of a certain event in the past ("what-where-when"). Firstly, we focused on a methodological comparison of standard psychological tests of episodic memory and a novel non-verbal computer-based Episodic-Like Memory Test (EMT) with several variants of varying difficulty, capable of discerning the memory for pictures, their sequence and position (Vlček et al., 2009). The second goal of our study was to demonstrate the applicability of the concept of episodic-like memory ("what- where-when") as a model in the testing of human episodic memory. Compared with other tests of episodic memory, EMT test does not depend on the verbalization of content. Contrasting the results obtained from EMT and other standard tests was, therefore, of interest. The results from the EMT test were compared across three age cohorts (N = 58; young, middle-aged, aged) of healthy volunteers. In the spatial domain of episodic-like...
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Neurobiologické koreláty paměti epizodického typu / Neurobiological Correlates of Episodic-like MemoryOravcová, Ivana January 2017 (has links)
Declarative memory is characterized as a conscious, explicit memory. Declarative memory consists of two essential systems, semantic memory and episodic memory. Episodic memory enables us to recall specific past events. A simplified model, so called Episodic-like memory is often used to study episodic memory mechanisms. According to this model, all events are stored in a contextual framework consisting of three basic components: identity of the object ('what' happened), temporal information ('when' it occurred) and spatial information ('where' did it happen). This type of memory is testable not only in humans but also in animal models. Aim of this diploma thesis is to study the neuronal substrate of individual components of episodic memory in healthy volunteers by means of functional magnetic resonance imaging (fMRI) and ecologically valid tasks designed in virtual reality environment. Results obtained in the fMRI paradigm show that apart from common neuronal substrate of episodic memory, additional brain structures are responsible for recollection of individual components of the episodic-like memory. Behavioral data indicate that the demands of the recollection of individual components is not equivalent. Additional analyses with parcellation of the brain to individual structures and consecutive...
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Ontogeneze episodické paměti u dětí předškolního věku / Ontogenesis of episodic memory in preschool childrenPíšová, Martina January 2020 (has links)
Episodic memory enables us to remember and recall life events from the past. Episodic memory is a specific type of long-term declarative memory, which undergoes changes in ontogeny. To examinate of episodic memory, "episodic-like memory model", was developed. This model focuses on three basic components of episodic memory: "What happened", "Where did it happen" and "When did it happen". The aim of this diploma thesis is to develop and to validate of particular tests of episodic memory with consideration for their feasibility for preschool children. In order to study episodic memory we used an "episodic-like memory model" and experiments which focused on: children's verbal ability, differentiation of two perspectives during remembering of events and timing memories on an autobiographical axis. We aimed to inspect the effect of age on performance in these tests, possible links between performance in these experiments and the effect of level and the three components of episodic memory on number of errors made. In our dataset we found a significant effect of the age of children in Sentence repetition test and in test of Object collection in the virtual house, in the same test we found a effect of the level on number of errors. We also found a significant correlation between correct responses in verbal...
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Vliv spánku na konsolidaci paměti epizodického typu u potkanů / The effect of sleep on consolidation of episodic-like memory in ratsPetránová, Erika January 2020 (has links)
We can notice the positive effects of sleep on many functions of our organism. For a long time we have observed the interconnection between sleep and memory and today we already know, that different sleep phases correlate with an improvement of different memory types. One of the hypotheses, that explain the positive effect of sleep on strengthening of the memory representations, is its irreplaceable active role in the process of memory consolidation. The memory consolidation of episodic type in animals, which processes memories into events with time and space context, could according to this theory occur due to two phase sleep process, in which each phase has a specific role. The theoretical part of this thesis will familiarize the reader with the problematic of organization of time and space in our brain, and introduce him to the foundations of electroencephalography (EEG) and offer a detailed introduction into the discussed hypothesis of active sleep consolidation. The practical part is then focused on the confirmation of the already mentioned hypothesis through the combination of comparison of results from the behavioral task of 2 groups of animals with different sleep manipulation and of the analysis of EEG signal recorded during the experiment before and after the training. The behavioral task...
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Recent and remote episodic-like memory : characteristics and circuits : approach via multi-site recordings of oscillatory activity in rat hippocampal and cortical brain regions / Mémoire épisodique récente et ancienne : caractéristiques et circuitsAllerborn, Marina 04 November 2016 (has links)
La mémoire épisodique, notre capacité de se rappeler des épisodes particuliers de notre vie, a été initialement définie chez l'homme en termes de l'information qu'elle contient, quel événement a eu lieu, où et dans quel contexte /quand s'est-il produit? La démonstration de l'existence de cette forme de mémoire chez l'animal a été réalisée chez le geais buissonnier. En effet, cet oiseau cacheur est capable de former une représentation mentale complexe du type de nourriture qu'il a caché, où et quand. Cette forme de mémoire qualifiée d' « episodic-like » a depuis une dizaine d'année été établie chez le rongeur. Au cours de ma thèse, j'ai suivi deux objectifs: valider un nouveau paradigme de mémoire épisodique chez le rat et l'utiliser pour étudier les circuits neuronaux qui sous-tendent cette forme particulière de mémoire. La première partie du manuscrit présente le développement et la validation d'un protocole original destiné à l'étude de la mémoire épisodique chez le rat. Lors de la conception de cette tâche, nous avons essayé de réduire au minimum la procédure d'entrainement des animaux afin de préserver l'essence même de la mémoire épisodique qui est la mémoire d'épisodes uniques. Pendant la tâche les rats ont été exposés à deux épisodes différents, au cours desquels des combinaisons uniques odeurs-place (information « quoi et où ») ont été présentées dans des contextes différents enrichis et multi-sensoriels (information « dans quel contexte »). Nous avons démontré que certains rats («ww») étaient capables de former des associations de mémoire (« episodic-like ») qui leur permettent de se souvenir de l'intégralité de l'épisode présenté après des délais courts (24h) et longs (24 jours) et dans différentes situations de rappel, tandis que d'autres («rest») ne se souvenaient que partiellement des informations présentes lors de l'épisode. Une approche pharmacologique réalisée lors de la validation de la tâche nous a permis de confirmer que l'hippocampe dorsal était nécessaire au rappel épisodique complet. Dans une version étendue du protocole dans laquelle des rats ont été exposés à deux épisodes supplémentaires, nous avons trouvé que l'expérience des épisodes préalablement acquis par les rats facilite l'encodage de nouveaux épisodes et que la mémoire de ces épisodes est plus stable. La deuxième partie de la thèse présente une première approche de l'étude des circuits neuronaux sous tendant la formation et la récupération de la mémoire épisodique. L'approche méthodologique utilisée est l'enregistrement multi-site de potentiels de champs locaux chez l'animal vigile. Le réseau de structures enregistrées inclut les aires sensorielles olfactives, des régions du cortex préfrontal médian et latéral ainsi que les régions dorsales et ventrales de l'hippocampe. Après avoir extrait des signaux le contenu fréquentiel dans deux bandes de fréquences (béta et théta), nous avons analysé les variations de puissance de l'activité oscillatoire dans ces bandes en utilisant des analyses en transformées de Hilbert et ondelette de Morlet. La période d'analyse est centrée sur l'échantillonnage de l'odeur, dernière information traitée avant que l'animal produise sa réponse comportementale. Les changements de puissance dans les deux bandes en réponse à l'odeur ont été comparés dans les différentes situations expérimentales pour les rats «ww» et les rats «rest». Les résultats obtenus montrent que le réseau de structures activées dans la bande béta en réponse à l'odeur est différent en fonction du profil de rappel des animaux (les rats du profil «ww» versus les rats «rest») à la fois en encodage et en situation de rappel. L'activité dans le réseau est également différente en fonction du type de réponse (hit versus rejet correct) / Episodic memory, our capacity to recollect particular life episodes, has been initially defined in terms of the information it contains, what kind of event, where and in which context/when did it take place. Pioneering studies on food-caching birds have demonstrated that animals are also able to form such complex memories, referred to as episodic-like memories in animals, however its modelling in rodents has proved challenging. The aim of this thesis was twofold: further development and validation in rats of a new episodic-like memory paradigm and study of neural circuits involved in formation and retrieval of this particular memory. The first part of the thesis presents the original behavioral paradigm developed in our group. In our task we tried to minimize training procedure in order to preserve the nature of episodic memory which is the memory for unique life episodes. Hereby rats were exposed to two different episodes, during which unique odor-place combinations (“what and where” information) were presented in different enriched multisensory contexts (“in which context” information). We found that some rats (“ww” group) were indeed able to form episodic-like memory associations which can be recalled after short (24 h) and long delays (24 days) in different experimental situations, while other animals (“rest” group) remembered only parts of the information contained in the initial episodes. Using pharmacological inactivation of dorsal hippocampus we have demonstrated that hippocampus is required specifically for retrieval of associated episodic-like memory information, but not for retrieval of single elements of the presented episodes in our task. In an extended version of the protocol in which rats were exposed to two additional episodes we found that previously acquired experience of the rats facilitates the encoding of new episodes and that the memory of these new episodes is more stable. The second part of the manuscript presents the first approach to study neural circuits involved in episodic-like memory encoding and retrieval in our task. Electrophysiological methodology was based on local field potential recordings obtained in parallel in several brain regions in behaving animals. The network of structures investigated included olfactory neocortical brain areas, brain regions in lateral and medial prefrontal cortex and the dorsal and ventral part of the hippocampus. The analysis was based on the estimation of magnitude of the oscillatory activity (described as power changes) in theta and beta frequency bands using Hilbert and Morlet wavelet transform for the analyses. The power analysis evolved around odor sampling event which constituted the last piece of information required for recollection of the whole episodic-like memory association. The odor-induced changes in power were compared between “ww” and “rest” animals in different experimental situations. We found that the network of activated brain regions in beta frequency band differed as a function of the memory profile of the rats (complete episodic-like memory recollection versus remembering partial information of the episodes) during both memory encoding as well as retrieval. We have also demonstrated that this active network changes when memory becomes consolidated (recent versus remote memory). Additionally we have shown that the activity in the network depends on the type of the response (hit versus correct rejection) given by the rat during memory encoding and retrieval. The network of brain regions that showed changes in theta power during memory formation and retrieval differed strongly from beta band network. In contrast to beta, the memory profile effect was much less prominent for theta band. However similarly to beta, there were also significant changes in network depending on the encoding session and the age of memory at test
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A cafe?na exerce efeitos positivos sobre a mem?ria tipo epis?dica em ratos adultos sem influenciar a sobreviv?ncia neural no giro denteadoMac?do, Priscila Tavares 27 April 2012 (has links)
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Previous issue date: 2012-04-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The caffeine is a mild psychostimulant that has positive cognitive effects at low doses, while promotes detrimental effects on these processes at higher doses. The episodic-like memory can be evaluated in rodents through hippocampus-dependent tasks. The dentate gyrus is a hippocampal subregion in which neurogenesis occurs in adults, and it is believed that this process is related to the function of patterns separation, such as the identification of spatial and temporal patterns when discriminating events. Furthermore, neurogenesis is influenced spatial and contextual learning tasks. Our goal was to evaluate the performance of male Wistar rats in episodic-like tasks after acute or chronic caffeine treatment (15mg/kg or 30mg/kg). Moreover, we assessed the chronic effect of the caffeine treatment, as well as the influence of the hippocampus-dependent learning tasks, on the survival of new-born neurons at the beginning of treatment. For this purpose, we used BrdU to label the new cells generated in the dentate gyrus. Regarding the acute treatment, we found that the saline group presented a tendency to have better spatial and temporal discrimination than caffeine groups. The chronic caffeine group 15 mg/kg (low dose) showed the best discrimination of the temporal aspect of episodic-like memory, whereas the chronic caffeine group 30mg/kg (high dose) was able to discriminate temporal order, only in a condition of greater difficulty. Assessment of neurogenesis using immunohistochemistry for evaluating survival of new-born neurons generated in the dentate gyrus revealed no difference among groups of chronic treatment. Thus, the positive mnemonic effects of the chronic caffeine treatment were not related to neuronal survival. However, another plastic mechanism could explain the positive mnemonic effect, given that there was no improvement in the acute caffeine groups / A cafe?na ? um leve psicoestimulante que em baixas doses tem efeitos cognitivos e mnem?nicos positivos, enquanto em altas doses tende a possuir efeitos prejudiciais sobre esses processos. A mem?ria tipo-epis?dica em roedores pode ser avaliada com tarefas hipocampo-dependentes. O giro denteado ? uma subregi?o hipocampal onde ocorre neurog?nese no adulto, e acredita-se que esse processo esteja relacionado ? sua fun??o de separa??o de padr?es, ou seja, identifica??o de padr?es espa?o-temporais para discriminar eventos. Al?m disso, a neurog?nese ? influenciada pelo aprendizado de tarefas espaciais e contextuais. Nosso objetivo foi avaliar os efeitos comportamentais em tarefas tipo-epis?dicas, em ratos Wistar machos, submetidos a tratamentos agudo ou cr?nico com cafe?na, nas doses de 15mg/kg ou 30mg/kg. Al?m disso, procuramos avaliar as rela??es do efeito cr?nico da cafe?na, em doses baixa e elevada, bem como da influ?ncia do aprendizado de tarefas hipocampo-dependentes, sobre a sobreviv?ncia de neur?nios nascidos no in?cio do tratamento, fazendo uso de BrdU para marcar novas c?lulas geradas no giro denteado. Quanto ao tratamento agudo, vimos que o grupo salina tendeu a apresentar melhor discrimina??o temporal e espacial que os grupos cafe?na, nas tarefas executadas. Os resultados do tratamento cr?nico mostraram que houve melhor discrimina??o do grupo cafe?na 15 mg/kg (dose baixa) quanto ao aspecto temporal da mem?ria epis?dica; j? o grupo cafe?na 30mg/kg (dose alta) conseguiu discriminar melhor temporalmente em condi??o de maior dificuldade de execu??o em compara??o a menor dificuldade. Avalia??o da neurog?nese por meio de imunohistoqu?mica para contagem de novos neur?nios gerados no giro denteado n?o revelou nenhuma diferen?a entre os grupos do tratamento cr?nico. Assim, os efeitos positivos mnem?nicos do tratamento cr?nico com cafe?na n?o est?o relacionados com a sobreviv?ncia neuronal. Entretanto, outro mecanismo pl?stico deve explicar o efeito mnem?nico positivo, haja vista que n?o houve melhora nos grupos tratados com cafe?na administrada agudamente
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