No description available.

Seres humanos com danos nos corpos mamilares exibem prejuízos no funcionamento da memória episódica. O presente estudo investigou a possível participação do núcleo mamilar medial (MM), estrutura densamente inervada por fibras imunorreativas ao hormônio concentrador de melanina (MCH) potencialmente envolvida no comportamento alimentar, em processos de evocação de memórias sobre locais em que alimento foi previamente encontrado, em ratos. Investigou-se ainda seu envolvimento na memória espacial motivada aversivamente, por meio do labirinto aquático de Morris, e em processos de ansiedade, por meio do labirinto em cruz elevado. Descreve-se uma tarefa comportamental envolvendo busca alimentar orientada por memória espacial em ratos, funcionalmente análoga ao teste de aprendizagem de pares associados, utilizado para avaliar memória episódica em seres humanos. Ratos treinados a escavar numa arena para obter alimento foram expostos ao pareamento de um determinado sabor, e.g., amendoim, com um local da arena e, numa segunda tentativa, ao pareamento de um outro sabor, e.g., avelã, com um local diferente da mesma arena. Antes de uma terceira tentativa, ainda na caixa de espera, os animais receberam uma amostra de amendoim ou avelã. Então, inseridos na arena para uma terceira tentativa, deveriam procurar e escavar por alimento enterrado no local sinalizado pela amostra. As associações sabor-local, a seqüência das associações, os locais do pareamento e a amostra oferecida antes da terceira tentativa, variaram quase aleatoriamente a cada dia. O treinamento dos animais para a aquisição da tarefa foi prolongado. O número de visitas e o tempo de permanência no local da arena sinalizado pela amostra foram significativamente maiores em relação aos parâmetros correspondentes ao local pareado com alimento mas não sinalizado pela amostra, quando o intervalo de tempo entre a 2ª e 3ª tentativas foi 60 ou 120 minutos; Testes de Avaliação sem oferta de alimento na arena na 3ª tentativa, permitiram excluir a hipótese de que os animais desempenharam essa tarefa com base em estímulos olfativos, levando à conclusão que o fizeram com base na memória das associações sabor-local. Ratos com danos seletivos do MM, induzidos pela aplicação tópica, micro-iontoforética, de N-Metil-D-Aspartato (NMDA), testados na tarefa de pares associados sabor-local, não exibiram prejuízo de desempenho em relação aos animais controle. Análises adicionais revelaram que houve uma redução da busca por alimento em ambos os grupos (lesado e controle) nos testes pós-operatórios, em relação ao seu próprio desempenho nos testes pré-operatórios; porém, essa redução foi mais acentuada em relação ao local sinalizado pela amostra, particularmente nos animais do grupo lesado. Estes resultados, embora não conclusivos, podem representar indícios em favor da idéia de que o MM estaria envolvido numa circuitaria relacionada à memória espacial voltada à busca alimentar. Mais estudos seriam necessários para avaliar essa possibilidade. Além disso, esses animais não exibiram qualquer prejuízo no teste de memória de referência espacial no labirinto aquático de Morris e no paradigma do teste e re-teste no labirinto em cruz elevado, sugerindo que esse tipo de lesão não leva a deficiência no funcionamento da memória espacial motivada por estimulação aversiva, na memória aversiva por espaços abertos ou nos mecanismos responsáveis pela ansiedade. / Human beings with damage to the mammillary bodies exhibit episodic memory disruption. This study investigated the potential participation of the medial mammillary nucleus (MM), a structure that receives a high density of melaninconcentrating hormone immunoreactive fibers (MCH) potentially involved in food intake, in processes of retrieval of memory about places where food was previously found, in rats. In addition, we investigated the possible involvement of this brain structure in both aversively motivated spatial memory, using the Morris´ water maze, and in anxiety, using the elevated plus maze. A behavioral task involving search for food guided by spatial memory, in rats, functionally analogous to the paired-associate learning task used for studying episodic memory in humans, was described. Rats trained to dig for food in an arena were exposed both to the pairing of a taste, peanut, with a specific place in the arena and, in a second trial, to the pairing of another taste, hazelnut, with another place in the arena. Immediately before a third trial, while still in the waiting box, the animals received a sample of either peanut or hazelnut. Then, they were inserted into the arena for a third trial and could search and dig for food buried in the place previously associated with the sample. The taste-place associations, sequence of associations, pairing places and sample offered before the third trial, were all varied quasi-randomly every day. The animals took extensive training to learn this task. It was found that the number of visits and the time spent in the place indicated by the sample were significantly greater as compared to the corresponding parameters of the place previously associated with a taste but not indicated by the sample, when the time interval between the second and the third trials was both 60 and 120 min; probe tests with no food in the arena in the third trial allowed to exclude the hypothesis that the rats were performing the task relying on olfactory cues, leading to the conclusion that the animals performed the task relying on the memory for the associations tastefood. Rats with selective damage to the MM, induced by topic, microiontophoretic, injections of N-Methyl-D-Aspartate (NMDA), tested in the taste-place pairedassociate learning task, did not exhibit any disruption of performance relative to the controls. Additional analyses revealed that both MM and control subjects exhibited a reduction of food search during the post-operatory tests as compared to their own performance in pre-operatory tests; however, this reduction was stronger towards the place indicated by the sample, particularly for the animals subjected to MM damage. Even though not conclusive, these results may suggest that the MM might be involved in search for food guided by spatial memory. More studies would be required to evaluate this possibility. Further, these rats did not exhibit any disruption of performance in the reference memory test in the water maze and in the test/re-test elevated plus maze, suggesting that this type of damage does not disrupt aversively motivated spatial memory, open-space aversive memory and anxiety.

Le syndrome de Coffin Lowry est une forme syndromique rare de déficience intellectuelle liée au chromosome X. Ce syndrome est dû à des mutations du gène Rsk2 codant la protéine kinase RSK2 dans la voie de signalisation des MAPK/ERK. La caractérisation phénotypique du modèle murin Rsk2-KO a principalement mis en évidence un retard d’acquisition ainsi qu’un déficit de mémoire spatiale à long terme, suggérant une altération des fonctions hippocampiques. Nous avons montré que les souris Rsk2-KO présentent également des déficits dans une forme d’apprentissage et de mémoire mettant en jeu la fonction de séparation de patterns dépendante du gyrus denté. Plusieurs études montrent que la genèse de nouveaux neurones dans le gyrus denté chez l’adulte constitue une forme de plasticité jouant un rôle important dans l’apprentissage et la mémoire dépendante de l’hippocampe, en particulier dans les tâches spatiales et de séparation de patterns. En raison des déficits observés chez les souris Rsk2-KO, nous nous sommes intéressés à la neurogenèse adulte chez ce modèle murin. Aucune différence de prolifération, de survie ou de maturation n’a été observée dans le gyrus denté des souris Rsk2-KO à l’état basal, ni après une tâche de séparation de patterns. Cependant, nous avons observé un déficit de survie des nouvelles cellules chez les souris Rsk2-KO après apprentissage dans la piscine de Morris. La littérature montre que l’enrichissement environnemental a des effets bénéfiques sur les performances cognitives des rongeurs et est notamment capable d’augmenter la neurogenèse adulte hippocampique. Nous avons donc analysé les effets de l’enrichissement sur les performances comportementales et la neurogenèse adulte des souris Rsk2-KO. Nos résultats montrent qu’un protocole d’enrichissement environnemental de 3 heures par jours durant 24 jours est capable de compenser ou d’améliorer les performances des souris Rsk2-KO dans les tâches de mémoire spatiale et de séparation de patterns et aussi d’augmenter la neurogenèse hippocampique adulte. / The Coffin-Lowry Syndrome is a rare syndromic form of X-linked intellectual disability. This syndrome is caused by mutations of the Rsk2 gene that encodes a protein kinase, RSK2, in the MAPK/ERK signaling pathway. Characterization of the behavioural phenotype of Rsk2-KO mice mainly showed that they display delayed acquisition and long-term deficits in a spatial reference memory task, suggesting an alteration in hippocampal function. Here, we show that Rsk2-KO mice are also deficient in a learning and memory task that involves dentate gyrus-dependent pattern separation function. Several studies showed the formation of new neurons in the adult dentate gyrus by neurogenesis is a form of plasticity that plays a significant role in hippocampal-dependent learning and memory, in particular for spatial learning and memory and pattern separation. As these functions are altered in Rsk2-KO mice, we studied hippocampal adult neurogenesis in these mice. No difference in proliferation, survival and maturation of newborn neurons was found in the dentate gyrus of the mutant mice in basal conditions, nor after a pattern separation task. However, we found a deficit in the survival of newborn cells in Rsk2-KO mice submitted to spatial learning and memory in the Morris water maze task. According to several studies, environmental enrichment in rodents has beneficial effects on cognitive performance and is associated with an enhancement of adult hippocampal neurogenesis. Thus, we assessed the potential effect of environmental enrichment on spatial learning and memory performance and adult hippocampal neurogenesis in Rsk2-KO mice. Our results show that an environmental enrichment protocol of 3h per day during 24 days can rescue or ameliorate spatial learning and memory performance and pattern separation function in Rsk2-KO mice and increase adult hippocampal neurogenesis.

Seres humanos com danos nos corpos mamilares exibem prejuízos no funcionamento da memória episódica. O presente estudo investigou a possível participação do núcleo mamilar medial (MM), estrutura densamente inervada por fibras imunorreativas ao hormônio concentrador de melanina (MCH) potencialmente envolvida no comportamento alimentar, em processos de evocação de memórias sobre locais em que alimento foi previamente encontrado, em ratos. Investigou-se ainda seu envolvimento na memória espacial motivada aversivamente, por meio do labirinto aquático de Morris, e em processos de ansiedade, por meio do labirinto em cruz elevado. Descreve-se uma tarefa comportamental envolvendo busca alimentar orientada por memória espacial em ratos, funcionalmente análoga ao teste de aprendizagem de pares associados, utilizado para avaliar memória episódica em seres humanos. Ratos treinados a escavar numa arena para obter alimento foram expostos ao pareamento de um determinado sabor, e.g., amendoim, com um local da arena e, numa segunda tentativa, ao pareamento de um outro sabor, e.g., avelã, com um local diferente da mesma arena. Antes de uma terceira tentativa, ainda na caixa de espera, os animais receberam uma amostra de amendoim ou avelã. Então, inseridos na arena para uma terceira tentativa, deveriam procurar e escavar por alimento enterrado no local sinalizado pela amostra. As associações sabor-local, a seqüência das associações, os locais do pareamento e a amostra oferecida antes da terceira tentativa, variaram quase aleatoriamente a cada dia. O treinamento dos animais para a aquisição da tarefa foi prolongado. O número de visitas e o tempo de permanência no local da arena sinalizado pela amostra foram significativamente maiores em relação aos parâmetros correspondentes ao local pareado com alimento mas não sinalizado pela amostra, quando o intervalo de tempo entre a 2ª e 3ª tentativas foi 60 ou 120 minutos; Testes de Avaliação sem oferta de alimento na arena na 3ª tentativa, permitiram excluir a hipótese de que os animais desempenharam essa tarefa com base em estímulos olfativos, levando à conclusão que o fizeram com base na memória das associações sabor-local. Ratos com danos seletivos do MM, induzidos pela aplicação tópica, micro-iontoforética, de N-Metil-D-Aspartato (NMDA), testados na tarefa de pares associados sabor-local, não exibiram prejuízo de desempenho em relação aos animais controle. Análises adicionais revelaram que houve uma redução da busca por alimento em ambos os grupos (lesado e controle) nos testes pós-operatórios, em relação ao seu próprio desempenho nos testes pré-operatórios; porém, essa redução foi mais acentuada em relação ao local sinalizado pela amostra, particularmente nos animais do grupo lesado. Estes resultados, embora não conclusivos, podem representar indícios em favor da idéia de que o MM estaria envolvido numa circuitaria relacionada à memória espacial voltada à busca alimentar. Mais estudos seriam necessários para avaliar essa possibilidade. Além disso, esses animais não exibiram qualquer prejuízo no teste de memória de referência espacial no labirinto aquático de Morris e no paradigma do teste e re-teste no labirinto em cruz elevado, sugerindo que esse tipo de lesão não leva a deficiência no funcionamento da memória espacial motivada por estimulação aversiva, na memória aversiva por espaços abertos ou nos mecanismos responsáveis pela ansiedade. / Human beings with damage to the mammillary bodies exhibit episodic memory disruption. This study investigated the potential participation of the medial mammillary nucleus (MM), a structure that receives a high density of melaninconcentrating hormone immunoreactive fibers (MCH) potentially involved in food intake, in processes of retrieval of memory about places where food was previously found, in rats. In addition, we investigated the possible involvement of this brain structure in both aversively motivated spatial memory, using the Morris´ water maze, and in anxiety, using the elevated plus maze. A behavioral task involving search for food guided by spatial memory, in rats, functionally analogous to the paired-associate learning task used for studying episodic memory in humans, was described. Rats trained to dig for food in an arena were exposed both to the pairing of a taste, peanut, with a specific place in the arena and, in a second trial, to the pairing of another taste, hazelnut, with another place in the arena. Immediately before a third trial, while still in the waiting box, the animals received a sample of either peanut or hazelnut. Then, they were inserted into the arena for a third trial and could search and dig for food buried in the place previously associated with the sample. The taste-place associations, sequence of associations, pairing places and sample offered before the third trial, were all varied quasi-randomly every day. The animals took extensive training to learn this task. It was found that the number of visits and the time spent in the place indicated by the sample were significantly greater as compared to the corresponding parameters of the place previously associated with a taste but not indicated by the sample, when the time interval between the second and the third trials was both 60 and 120 min; probe tests with no food in the arena in the third trial allowed to exclude the hypothesis that the rats were performing the task relying on olfactory cues, leading to the conclusion that the animals performed the task relying on the memory for the associations tastefood. Rats with selective damage to the MM, induced by topic, microiontophoretic, injections of N-Methyl-D-Aspartate (NMDA), tested in the taste-place pairedassociate learning task, did not exhibit any disruption of performance relative to the controls. Additional analyses revealed that both MM and control subjects exhibited a reduction of food search during the post-operatory tests as compared to their own performance in pre-operatory tests; however, this reduction was stronger towards the place indicated by the sample, particularly for the animals subjected to MM damage. Even though not conclusive, these results may suggest that the MM might be involved in search for food guided by spatial memory. More studies would be required to evaluate this possibility. Further, these rats did not exhibit any disruption of performance in the reference memory test in the water maze and in the test/re-test elevated plus maze, suggesting that this type of damage does not disrupt aversively motivated spatial memory, open-space aversive memory and anxiety.

Genericamente, esta tese busca identificar a relação entre arquitetura e cultura de consumo, como definidora da identidade da arquitetura moderna de Miami no segundo pós-guerra. O conceito de cidade-balneário de Miami Beach foi transformado durante o decorrer da sua história. Os seus hotéis de inverno de meados da década de 1910 até 1945--destinados aos milionários associados à indústria automobilística--dão lugar a uma nova tipologia de hotel no pós-guerra, o hotelbalneário para a classe média norte-americana. Especificamente, este trabalho analisa os hotéis-balneários de Morris Lapidus (1902-2001) em Miami Beach na década de 1950, que definem a identidade da arquitetura moderna da cidade e que, por sua vez, caracterizam a sua própria imagem como cidade-balneário. A obra do setor da hospitalidade de Lapidus surge como informante de uma arquitetura com atenção máxima à escala humana do usuário. Suas lojas, construídas na época da Depressão, e seus hotéis do segundo pós-guerra, meticulosamente projetados para a classe média, surgem como veículos que contribuíram para a formação da cultura nacionalista, otimista e progressista, incentivada pelo governo federal de Franklin Roosevelt nesses períodos históricos. A histórica polêmica gerada sobre essa obra hoteleira de Lapidus, associada aos paradoxos presentes na composição arquitetônica de seus edifícios, está dividida entre a dogmática interpretação moderna do International Style e a leitura pós-moderna centrada na recuperação humanista. A narrativa da tese está fundamentada nessa polêmica cujo cerne está na questão sobre gosto e qualidade em arquitetura instigada por essa obra controversa. Este trabalho interpreta os paradoxos desses hotéis-balneários como uma metodologia de projeto de Lapidus, centrada na dialética de elementos de projeto contrastantes. Dessa dialética compositiva, nasce uma arquitetura híbrida, acessível à emergente classe-média, consumista e móvel, do pós-guerra. Esse hibridismo é estrategicamente elaborado como metodologia de projeto--uma colagem. A arquitetura como colagem nasce das escolhas de elementos extraídos de fontes diversas, que são apropriados e recriados pelo arquiteto. A diversidade de fontes de projeto advém da circulação de ideias--exposições, publicações e viagens. O apogeu da carreira de Lapidus é o hotel Fontainebleau (1954), o primeiro edifício do arquiteto de interiores que foi validado pelo seu conjunto de lojas da Main Street norte-americana. Os interiores derivam do método de projeto desenvolvido para as suas lojas, enquanto que a arquitetura do Fontainebleau descende da obra formativa de Oscar Niemeyer. A arquitetura moderna tropical do edifício contribuiu para a tipologia de hotel-balneário de Miami Beach no segundo pósguerra que, por sua vez, redefiniu o seu conceito de cidade-balneário. Após meio século, a arquitetura moderna hoteleira de Miami, originada com o Fontainebleau, está \"preservada\" sob a denominação Miami Modern-MiMo. No terceiro milênio, o MiMo, transformado em \"marca\" de consumo, é o veículo imobiliário da preservação da arquitetura moderna de Miami. / Generally, this dissertation aims at identifying the relationship between architecture and consumer culture, which defines the identity of Miami\'s modern architecture in the second post-war. The concept of Miami Beach as a seaside resort has been transformed throughout its history. Its winter hotels from the mid-1910s to 1945--intended for the auto industry millionaires--are replaced by a new typology of post-war hotel, the hotel-resort for the American middle class. Specifically, this work examines Morris Lapidus (1902-2001)\' hotel-resorts in Miami Beach in the 1950s, which define the identity of the city\'s modern architecture and which, in turn, characterizes the image of the city as a seaside resort. Lapidus\' hospitality industry work emerges as an informant of an architecture with maximum attention on the user\'s human scale. Its stores, built in the Depression era, and its post-war hotels for the middle class, both meticulously designed, have emerged as vehicles that contributed to the formation of the optimistic and progressive nationalist culture encouraged by the Franklin Roosevelt federal government in these historic periods. The historical polemic generated on such Lapidus\' hotel work, associated with the paradoxes present in the architectural design composition of its buildings, is divided between the dogmatic modern interpretation of the International Style and the postmodern review, centered on the rediscovery of humanism. The narrative of the thesis is based on this controversy, whose core is the question about taste and quality in architecture instigated by this controversial work. This work interprets the paradoxes of these hotel-resorts as a Lapidus\' design methodology, centered on the dialectic of contrasting design elements. From this compositional dialectic, a hybrid architecture is formed, accessible to the emerging middle-class, consumerist and mobile, of the second postwar. This hybridism is strategically planned as a design methodology--a collage. Architecture as collage is assembled from the choices of elements drawn from diverse sources, which are appropriated and recreated by the architect. The diversity of project sources comes from the circularity of ideas--exhibitions, publications, and travel. The heyday of Lapidus\' career as an architect is the Fontainebleau Hotel (1954), the first building by the then interior designer, who was validated by its collection of American Main Street stores designed during the Depression. The Fontainebleau Hotel interiors are derived from the design method developed for his stores, while its architecture descends from the formative work of the Brazilian architect Oscar Niemeyer. The tropical modern architecture of the Fontainebleau established the typology of the post-war Miami Beach hotel-resort, which in turn redefined its seaside resort concept. After half a century, Miami\'s modern hotel architecture, originated with the Fontainebleau Hotel, is \"preserved\" under the slogan Miami Modern-MiMo. In the third millennium, the MiMo, transformed into a consumer brand, is the real estate vehicle for the preservation of the modern architecture in Miami.

Genericamente, esta tese busca identificar a relação entre arquitetura e cultura de consumo, como definidora da identidade da arquitetura moderna de Miami no segundo pós-guerra. O conceito de cidade-balneário de Miami Beach foi transformado durante o decorrer da sua história. Os seus hotéis de inverno de meados da década de 1910 até 1945--destinados aos milionários associados à indústria automobilística--dão lugar a uma nova tipologia de hotel no pós-guerra, o hotelbalneário para a classe média norte-americana. Especificamente, este trabalho analisa os hotéis-balneários de Morris Lapidus (1902-2001) em Miami Beach na década de 1950, que definem a identidade da arquitetura moderna da cidade e que, por sua vez, caracterizam a sua própria imagem como cidade-balneário. A obra do setor da hospitalidade de Lapidus surge como informante de uma arquitetura com atenção máxima à escala humana do usuário. Suas lojas, construídas na época da Depressão, e seus hotéis do segundo pós-guerra, meticulosamente projetados para a classe média, surgem como veículos que contribuíram para a formação da cultura nacionalista, otimista e progressista, incentivada pelo governo federal de Franklin Roosevelt nesses períodos históricos. A histórica polêmica gerada sobre essa obra hoteleira de Lapidus, associada aos paradoxos presentes na composição arquitetônica de seus edifícios, está dividida entre a dogmática interpretação moderna do International Style e a leitura pós-moderna centrada na recuperação humanista. A narrativa da tese está fundamentada nessa polêmica cujo cerne está na questão sobre gosto e qualidade em arquitetura instigada por essa obra controversa. Este trabalho interpreta os paradoxos desses hotéis-balneários como uma metodologia de projeto de Lapidus, centrada na dialética de elementos de projeto contrastantes. Dessa dialética compositiva, nasce uma arquitetura híbrida, acessível à emergente classe-média, consumista e móvel, do pós-guerra. Esse hibridismo é estrategicamente elaborado como metodologia de projeto--uma colagem. A arquitetura como colagem nasce das escolhas de elementos extraídos de fontes diversas, que são apropriados e recriados pelo arquiteto. A diversidade de fontes de projeto advém da circulação de ideias--exposições, publicações e viagens. O apogeu da carreira de Lapidus é o hotel Fontainebleau (1954), o primeiro edifício do arquiteto de interiores que foi validado pelo seu conjunto de lojas da Main Street norte-americana. Os interiores derivam do método de projeto desenvolvido para as suas lojas, enquanto que a arquitetura do Fontainebleau descende da obra formativa de Oscar Niemeyer. A arquitetura moderna tropical do edifício contribuiu para a tipologia de hotel-balneário de Miami Beach no segundo pósguerra que, por sua vez, redefiniu o seu conceito de cidade-balneário. Após meio século, a arquitetura moderna hoteleira de Miami, originada com o Fontainebleau, está \"preservada\" sob a denominação Miami Modern-MiMo. No terceiro milênio, o MiMo, transformado em \"marca\" de consumo, é o veículo imobiliário da preservação da arquitetura moderna de Miami. / Generally, this dissertation aims at identifying the relationship between architecture and consumer culture, which defines the identity of Miami\'s modern architecture in the second post-war. The concept of Miami Beach as a seaside resort has been transformed throughout its history. Its winter hotels from the mid-1910s to 1945--intended for the auto industry millionaires--are replaced by a new typology of post-war hotel, the hotel-resort for the American middle class. Specifically, this work examines Morris Lapidus (1902-2001)\' hotel-resorts in Miami Beach in the 1950s, which define the identity of the city\'s modern architecture and which, in turn, characterizes the image of the city as a seaside resort. Lapidus\' hospitality industry work emerges as an informant of an architecture with maximum attention on the user\'s human scale. Its stores, built in the Depression era, and its post-war hotels for the middle class, both meticulously designed, have emerged as vehicles that contributed to the formation of the optimistic and progressive nationalist culture encouraged by the Franklin Roosevelt federal government in these historic periods. The historical polemic generated on such Lapidus\' hotel work, associated with the paradoxes present in the architectural design composition of its buildings, is divided between the dogmatic modern interpretation of the International Style and the postmodern review, centered on the rediscovery of humanism. The narrative of the thesis is based on this controversy, whose core is the question about taste and quality in architecture instigated by this controversial work. This work interprets the paradoxes of these hotel-resorts as a Lapidus\' design methodology, centered on the dialectic of contrasting design elements. From this compositional dialectic, a hybrid architecture is formed, accessible to the emerging middle-class, consumerist and mobile, of the second postwar. This hybridism is strategically planned as a design methodology--a collage. Architecture as collage is assembled from the choices of elements drawn from diverse sources, which are appropriated and recreated by the architect. The diversity of project sources comes from the circularity of ideas--exhibitions, publications, and travel. The heyday of Lapidus\' career as an architect is the Fontainebleau Hotel (1954), the first building by the then interior designer, who was validated by its collection of American Main Street stores designed during the Depression. The Fontainebleau Hotel interiors are derived from the design method developed for his stores, while its architecture descends from the formative work of the Brazilian architect Oscar Niemeyer. The tropical modern architecture of the Fontainebleau established the typology of the post-war Miami Beach hotel-resort, which in turn redefined its seaside resort concept. After half a century, Miami\'s modern hotel architecture, originated with the Fontainebleau Hotel, is \"preserved\" under the slogan Miami Modern-MiMo. In the third millennium, the MiMo, transformed into a consumer brand, is the real estate vehicle for the preservation of the modern architecture in Miami.

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Die vorliegende Arbeit behandelt die kollektive Dynamik identischer Klasse-I-anregbarer Elemente. Diese können im Rahmen der nichtlinearen Dynamik als Systeme nahe einer Sattel-Knoten-Bifurkation auf einem invarianten Kreis beschrieben werden. Der Fokus der Arbeit liegt auf dem Studium aktiver Rotatoren als Prototypen solcher Elemente. In Teil eins der Arbeit besprechen wir das klassische Modell abstoßend gekoppelter aktiver Rotatoren von Shinomoto und Kuramoto und generalisieren es indem wir höhere Fourier-Moden in der internen Dynamik der Rotatoren berücksichtigen. Wir besprechen außerdem die mathematischen Methoden die wir zur Untersuchung des Aktive-Rotatoren-Modells verwenden. In Teil zwei untersuchen wir Existenz und Stabilität periodischer Zwei-Cluster-Lösungen für generalisierte aktive Rotatoren und beweisen anschließend die Existenz eines Kontinuums periodischer Lösungen für eine Klasse Watanabe-Strogatz-integrabler Systeme zu denen insbesondere das klassische Aktive-Rotatoren-Modell gehört und zeigen dass (i) das Kontinuum eine normal-anziehende invariante Mannigfaltigkeit bildet und (ii) eine der auftretenden periodischen Lösungen Splay-State-Dynamik besitzt. Danach entwickeln wir mit Hilfe der Averaging-Methode eine Störungstheorie für solche Systeme. Mit dieser können wir Rückschlüsse auf die asymptotische Dynamik des generalisierten Aktive-Rotatoren-Modells ziehen. Als Hauptergebnis stellen wir fest dass sowohl periodische Zwei-Cluster-Lösungen als auch Splay States robuste Lösungen für das Aktive-Rotatoren-Modell darstellen. Wir untersuchen außerdem einen "Stabilitätstransfer" zwischen diesen Lösungen durch sogenannte Broken-Symmetry States. In Teil drei untersuchen wir Ensembles gekoppelter Morris-Lecar-Neuronen und stellen fest, dass deren asymptotische Dynamik der der aktiven Rotatoren vergleichbar ist was nahelegt dass die Ergebnisse aus Teil zwei ein qualitatives Bild für solch kompliziertere und realistischere Neuronenmodelle liefern. / We study the collective dynamics of class I excitable elements, which can be described within the theory of nonlinear dynamics as systems close to a saddle-node bifurcation on an invariant circle. The focus of the thesis lies on the study of active rotators as a prototype for such elements. In part one of the thesis, we motivate the classic model of repulsively coupled active rotators by Shinomoto and Kuramoto and generalize it by considering higher-order Fourier modes in the on-site dynamics of the rotators. We also discuss the mathematical methods which our work relies on, in particular the concept of Watanabe-Strogatz (WS) integrability which allows to describe systems of identical angular variables in terms of Möbius transformations. In part two, we investigate the existence and stability of periodic two-cluster states for generalized active rotators and prove the existence of a continuum of periodic orbits for a class of WS-integrable systems which includes, in particular, the classic active rotator model. We show that (i) this continuum constitutes a normally attracting invariant manifold and that (ii) one of the solutions yields splay state dynamics. We then develop a perturbation theory for such systems, based on the averaging method. By this approach, we can deduce the asymptotic dynamics of the generalized active rotator model. As a main result, we find that periodic two-cluster states and splay states are robust periodic solutions for systems of identical active rotators. We also investigate a 'transfer of stability' between these solutions by means of so-called broken-symmetry states. In part three, we study ensembles of higher-dimensional class I excitable elements in the form of Morris-Lecar neurons and find the asymptotic dynamics of such systems to be similar to those of active rotators, which suggests that our results from part two yield a suitable qualitative description for more complicated and realistic neural models.

本實驗室於先前利用莫氏水迷津試驗篩選學習快與學習慢的大白鼠，取出其海馬迴組織並進行聚合酶連鎖反應差異顯示(PCR differential display)，結果顯示學習快與學習慢的大白鼠背側海馬迴之間共有98個cDNA片段有差異表現。把這些cDNA片段進行定序並利用BLAST資料庫比對，其中一個cDNA片段為大白鼠的pias1 [protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1)] 基因。為了瞭解pias1基因的表現是否和空間學習有所關聯，隨機把大白鼠分成兩組，一組為有訓練組別(有空間線索與隱藏式平台)，另一組為無訓練的組別(沒有平台，作為游泳的控制組)同時進行莫氏水迷津學習試驗。試驗完畢，取出海馬迴組織進行即時定量聚合酶連鎖反應與西方墨點法來分析PIAS1的mRNA與蛋白質的表現。結果顯示有水迷津訓練的大白鼠，其PIAS1的mRNA與蛋白質表現皆明顯的高於無訓練的組別。為了更進一步確認PIAS1在空間學習中所扮演的角色，我們利用基因轉染的技術，轉染PIAS1 siRNA至大白鼠海馬迴CA1區域抑制PIAS1的表現。我們發現轉染PIAS1 siRNA至CA1區域會抑制大白鼠在水迷津的行為表現，然而轉染野生型的PIAS1質體基因至CA1區域卻會增進水迷津試驗的學習能力，同時我們也以西方墨點法發現，當轉染PIAS1 siRNA會增加STAT1 Tyr701的磷酸化，而轉染PIAS1 WT則會抑制STAT1 Tyr701的磷酸化。為了探討PIAS1促進記憶形成的分子機制，我們發現當轉染突變型的STAT1 Y701F質體基因至CA1區域，會抑制PIAS1 siRNA所造成記憶的損害。這些實驗結果代表著PIAS1會抑制STAT1 Tyr701的磷酸化，而PIAS1促進記憶的形成可能是藉由抑制STAT1 Tyr701的磷酸化而達成。另外，我們也單獨轉染突變型的STAT1 Y701F質體基因至CA1區域，水迷津實驗結果顯示會促進空間記憶的形成。目前PIAS1在免疫的角色已有許多研究證實，但是本篇研究是第一個提出PIAS1會參與哺乳類動物學習與記憶形成探討。 / Our laboratory has previously identified 98 cDNA fragments by using PCR differential display from rat dorsal hippocampus that are differentially expressed between fast learners and slow learners from the water maze learning task. After sequencing and BLAST analysis, one of these cDNA fragments encodes the rat pias1 [protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1)] gene. In order to determine whether pias1 gene expression is associated with spatial learning, naïve rats were randomly assigned to the trained group (with visual cues and platform been present) and the non-trained group (without the platform as the swimming control). The dorsal hippocampus from these animals was dissected out at the end of the training and was subjected to RNA and protein extraction for real-time PCR and Western blot analysis of PIAS1 expression, respectively. Results revealed that the pias1 mRNA level and protein level was both higher in the hippocampus of trained rats than non-trained rats. To further examine the role of PIAS1 involved in spatial learning and memory, the specific PIAS1 siRNA was used to knockdown the expression of PIAS1 in rat hippocampal CA1 region. We found that transfection of PIAS1 siRNA to the CA1 area impaired water maze performance, whereas transfection of the wild-type PIAS1 DNA plasmid to the CA1 area facilitated water maze performance in rats. Meanwhile, PIAS1 siRNA increased STAT1 phosphorylation at Tyr701 whereas PIAS1 WT decreased STAT1 phosphorylation at this residue. In the examination of molecular mechanism underlying PIAS1-mediated memory facilitation, we have found that transfection of the STAT1 Y701F mutant plasmid antagonized the memory-impairing effect of PIAS1 siRNA, whereas transfection of STAT1 Y701F alone facilitated spatial memory formation. These results together suggest that one of the molecular mechanisms underlying PIAS1-mediated memory facilitation is through decreased STAT1 phosphorylation at Tyr701. All these manipulations did not affect visible platform learning in rats. In addition to the well documented role of PIAS1 in the immune system, here we have been the first to demonstrate a novel role of PIAS1 involved in spatial memory formation in rats.