1 / Amanda Rosemary Pahng

京都大学 / 新制・課程博士 / 博士(薬科学) / 甲第23842号 / 薬科博第157号 / 新制||薬科||17(附属図書館) / 京都大学大学院薬学研究科医薬創成情報科学専攻 / (主査)教授 土居 雅夫, 教授 竹島 浩, 教授 中山 和久 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

This thesis examines the formation of national memory by exploring tenth anniversary television coverage of 9/11. By analyzing themes of nationalism that structure the television specials and create a positive national memory, this thesis argues that the national memory of 9/11 serves current national goals and develops myths of American exceptionalism while it ignores the negative consequences and realities of 9/11.

In everybody’s lives, there are strong emotional or surprising events that, for being special, are vividly remembered for a lifetime. Sometimes, these memories include one-shot images or details of associated daily life events that, for being ordinary, should have been rapidly forgotten. Why and how does the brain form and retain detailed memories of trivial events? The synaptic tagging and capture (STC) hypothesis of memory formation (Frey & Morris, Nature 1997) provides a theoretical framework that might explain the formation of these flashbulb memories at a cellular level. The hypothesis suggests that strong events, producing long-lasting memories, might stabilise memory for weak events by up-regulating the synthesis of late-phase plasticity-related proteins in neurons encoding memory traces for both events. This thesis tests this prediction of the STC hypothesis during the formation of long-term place memory in rodents. First, two new behavioural tasks are developed which provide sensitive measures of rapidly acquired place memory persistence - a new one-trial place memory task in the “event arena” and a modified delayed matching-to-place (DMP) protocol in the watermaze. Persistence of place memory is assessed and compared in these tasks. Given the important role of NMDA receptor activation during STC mechanisms, the contribution of NMDA and AMPA receptor activation in the hippocampus for the encoding and retrieval of place memory, respectively, is also established. Finally, weak and strong encoding events, leading to the formation of either shortor long-lasting place memory in the watermaze DMP task, are characterized. A second series of experiments investigates the possibility of synergistic interactions between different encoding events that occur in two different watermazes. First, weak and strong encoding events are arranged to occur within a short time-window to test behavioural analogues of the “strong-before-weak” and “weak-before-strong” STC paradigms characterised in electrophysiological experiments in rat hippocampal slices (Frey and Morris, 1997, 1998b). Then, after establishing i) the time course and local specificity of protein synthesis inhibition by intra-hippocampal infusion of anisomycin in vivo, ii) the dependence of long-term memory for strong encoding events on protein synthesis in the hippocampus, and iii) the induction of transcriptional and translational mechanisms in the hippocampus by strong encoding events, a behavioural analogue of the “strong-before-strong” STC paradigm (Frey and Morris, 1997) is also investigated. The results of these experiments are supportive of i) a role for hippocampal NMDA receptor-mediated synaptic plasticity in the encoding of rapidly acquired place memory; ii) a role for hippocampal AMPA receptor-mediated synaptic transmission in both encoding and retrieval of memory; and iii) a role for transcriptional and translational mechanisms in the hippocampus in the stabilisation of place memory. However, no evidence could be found supporting the involvement of synaptic tagging and capture mechanisms during the formation of long-lasting place memory.

京都大学 / 新制・課程博士 / 博士(医科学) / 甲第23115号 / 医科博第126号 / 新制||医科||8(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 伊佐 正, 教授 髙橋 良輔, 教授 井上 治久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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This thesis investigates how through experience the brain acquires and stores memories, and uses these to extract and modify knowledge. This question is being studied by both computational and experimental neuroscientists as it is of relevance for neuroscience, but also for artificial systems that need to develop knowledge about the world from limited, sequential data. It is widely assumed that new memories are initially stored in the hippocampus, and later are slowly reorganised into distributed cortical networks that represent knowledge. This memory reorganisation is called systems consolidation. In recent years, experimental studies have revealed complex hippocampal-neocortical interactions that have blurred the lines between the two memory systems, challenging the traditional understanding of memory processes. In particular, the prior existence of cortical knowledge frameworks (also known as schemas) was found to speed up learning and consolidation, which seemingly is at odds with previous models of systems consolidation. However, the underlying mechanisms of this effect are not known. In this work, we present a computational framework to explore potential interactions between the hippocampus, the prefrontal cortex, and associative cortical areas during learning as well as during sleep. To model the associative cortical areas, where the memories are gradually consolidated, we have implemented an artificial neural network (Restricted Boltzmann Machine) so as to get insight into potential neural mechanisms of memory acquisition, recall, and consolidation. We analyse the network's properties using two tasks inspired by neuroscience experiments. The network gradually built a semantic schema in the associative cortical areas through the consolidation of multiple related memories, a process promoted by hippocampal-driven replay during sleep. To explain the experimental data we suggest that, as the neocortical schema develops, the prefrontal cortex extracts characteristics shared across multiple memories. We call this information meta-schema. In our model, the semantic schema and meta-schema in the neocortex are used to compute consistency, conflict and novelty signals. We propose that the prefrontal cortex uses these signals to modulate memory formation in the hippocampus during learning, which in turn influences consolidation during sleep replay. Together, these results provide theoretical framework to explain experimental findings and produce predictions for hippocampal-neocortical interactions during learning and systems consolidation.

The zebrafish (Danio rerio) promises to meet the growing needs of gerontological and neurobehavioral research by possessing highly conserved anatomy and physiology with all other vertebrates, while having low maintenance costs and requiring only simple care. The neurological and physiological bases of learning, memory formation, and memory retention have been studied in a variety of model organisms, such as the rat, mouse, sheep, and several teleost fishes, the notable example being the zebrafish. Unfortunately, most of these animals are poorly suited to senescence research due to costs, care requirements, or long life spans. My research expands upon our rapidly growing understanding of zebrafish neurobiology, learning processes, sensory modalities, and memory retention. Two pairs of distinct aversive conditioning experiments using classic shuttlebox designs compared the effects of sensory modality and conditioned-unconditioned stimulus (CS-US) intervals, the time delay between application of conditioned sensory stimulus and delivery of the stressful unconditioned stimulus in the event of failure to avoid it, upon memory formation and retention. These studies yielded a general spectrum of results against which future conditioning studies may be compared. Both visual and olfactory stimuli were tested, as were 10 second and 15 second CS-US intervals. Successes were scored when the fish crossed the shuttlebox hurtle within the CS-US interval, thereby avoiding the negative unconditioned stimulus. After a three-month delay, ten additional trials were conducted to compare the long-term memory retention resulting from each protocol. When testing a 15s CS-US interval, olfactory conditioning was significantly more likely (39%) to produce a successful outcome (memory formation) than visual conditioning. Grouped results reveal that the second pair of experiments, each with a 10s CS-US interval, yielded significantly more successful memory formation than a 15s CS-US interval. A significant difference was found when comparing the results of any two experiments, except between the results of the visual and olfactory 10s interval experiments). Only the olfactory experiment using a 15s CS-US interval yielded memory retention results significantly higher than the mean of memory retention results from the four experiments. These findings offer inconclusive evidence supporting olfaction’s strong role in memory formation and retention in zebrafish. The results expand our understanding of the relationship between the olfactory and visual senses and memory in the zebrafish and indicate the olfactory sense’s key role in vertebrate neurobiology, warranting further research into the effects of aging on the olfactory-memory modality.

Memory formation in Drosophila melanogaster is composed of two pathways that are genetically distinct, and functionally independent of each other. These are short-term and long-term memory. Short-term memory is a transient phenomenon, located in the cytoplasm of the neuronal cells, which requires no alteration of gene expression. The formation of long-term memory requires a change in gene expression, therefore chromatin-modifying complexes may play an integral part. The mushroom-bodies of Drosophila are a distinct bilateral brain structure and are essential for the formation and recollection of long-term memory. Therefore, an alteration in gene expression within the mushroom bodies is essential to the formation of long-term memory. Disruption of a gene within the mushroom-bodies that resulted in an alteration in the formation of long-term memory would indicate that the gene is involved in long-term memory. In order to investigate the role of the two chromatin-modifying proteins, HDACX and pr-Set7, whose role in memory function is unknown, RNA interference was used to knockdown expression of their respective mRNA. Published GAL4 lines were used to drive down expression in the mushroom bodies. The efficacy of the knockdown on levels of mRNA was measured by quantitative RT-PCR. The effect of these knockdowns on the formation of long-term memory was assayed using conditioned courtship. Additionally, the actual spatial and temporal expression of the GAL4 drivers was investigated using fluorescent proteins, and analysed using fluorescent microscopy. Both pr-set7 and HDACX appear to play a role in long-term memory function. The RNAi-induced knockdown of the individual mRNAs caused impairment in long-term memory formation, although the exact mode of action is still to be elucidated. The levels of mRNA from these knockdowns were reduced within the head, although not to the extent expected. The fluorescent microscopy analysis indicated that the expression of mushroom-body specific GAL4 drivers was more widespread than previously reported.

Made available in DSpace on 2016-08-17T13:54:36Z (GMT). No. of bitstreams: 1 socorro paixao.pdf: 493112 bytes, checksum: f445bf553b67679556b7a91cbb5fbc10 (MD5) Previous issue date: 2006-01-18 / Analysis continual education of pedagogical coordinators from Secretaria Municipal de Educação, São Luís - SEMED - in the period from 2002 to 2004, which had as its basic proposal, lettered situations. To carry on this research, as analysis indicators, there were representations of the involved subjects in the molding process. The representations were identified through memory formation, built up by pedagogical coordinators, selected randomly, for sample. Besides these representations, we tried to reveal the representations present in the texts published by SEMED and in the speech of subjects responsible for planning, implantation and evaluation of the continual development proposal. After the confrontations of the representations it s possible to identify some patterns that characterize and found the investigated continual education. To carry out this socio-pedagogical study we had as support Moscovici, Bourdieu, Piaget and Chartier in the international field and in the national field we had Pereira, Bianchetti, Magda Soares, Farias and Cardoso beyond the documents elaborated by the continual education. It was made a qualitative investigation and an observation study of case dialoguing to the relevant theoretical production to the elected categories. / Análise da formação continuada de coordenadoras e de coordenadores pedagógicos da Secretaria Municipal de Educação de São Luís-MA- SEMED - no período de 2002 a 2004, que tinha como proposta básica situações de letramento. Para a realização deste estudo foram utilizadas, como indicadores de análises, as representações de sujeitos envolvidos no processo formativo. As representações foram identificadas através de Memoriais de formação, construídos por coordenadoras e coordenadores pedagógicos, selecionados aleatoriamente, para amostra. Além destas representações, buscamos desvelar as representações presentes nos textos editados pela SEMED e nos discursos de sujeitos responsáveis pelo planejamento, implementação e avaliação da proposta de formação continuada. As representações, ao serem confrontadas, identificaram os possíveis paradigmas que caracterizam e fundamentam a formação continuada investigada. Neste estudo sócio-pedagógico contamos com o apoio de Moscovici, Bourdieu, Piaget e Chartier, no campo internacional e com Pereira, Bianchetti, Magda Soares, Farias e Cardoso, no campo nacional, ao lado da documentação produto da formação continuada. Nossa opção investigativa de abordagem qualitativa se processou como um estudo de caso de observação, dialogando com a produção teórica pertinente às categorias eleitas.