Previous research on the relationship between spatial memory and adult hippocampal neurogenesis has been controversial. In the present study, neurogenesis was compared between two natural populations of the same species that differ in their reliance on spatial memory to cache and retrieve stored food. Western red squirrels store food in a single site whereas eastern red squirrels store food in multiple sites. Neurogenesis was assessed using endogenous markers of the number of proliferating cells (Ki-67) and the number of immature neurons (DCX), and neuronal recruitment was determined by measuring the area of the dentate gyrus of the hippocampus. The number of proliferating cells, immature neurons and neuronal recruitment were enhanced in the eastern compared to the western red squirrels, reflecting the food storing strategies used by the squirrels. This suggests that there is a positive correlation between adult hippocampal neurogenesis and spatial learning and memory.

Hypothermia therapy (HT) is used clinically following global cerebral ischemia (GCI) but its therapeutic mechanisms are not completely understood. An elucidation of such mechanisms may lead to novel therapeutic approaches that improve patient outcome. Using a murine model of GCI, we determined the effect of HT on the expression of inflammatory proteins in the hippocampus and serum. We also examined its effect on microglia/macrophage activation and neurodegeneration in the brain at 72 hours following ischemia, and its effect on long-term spatial memory/learning and contextual fear response. GCI led to increased neurodegeneration and microglia/macrophage activation in the hippocampus, and increased IL-1β and KC protein expression in the hippocampus at 72 hours. Hypothermia therapy attenuated these inflammatory responses. It also improved spatial learning/memory at 7 and 21 days, and preserved contextual fear response 21 days post-ischemia. Hypothermia therapy attenuated the post-ischemic inflammatory response, protected hippocampal neurons, and preserved long-term memory and learning.

Hypothermia therapy (HT) is used clinically following global cerebral ischemia (GCI) but its therapeutic mechanisms are not completely understood. An elucidation of such mechanisms may lead to novel therapeutic approaches that improve patient outcome. Using a murine model of GCI, we determined the effect of HT on the expression of inflammatory proteins in the hippocampus and serum. We also examined its effect on microglia/macrophage activation and neurodegeneration in the brain at 72 hours following ischemia, and its effect on long-term spatial memory/learning and contextual fear response. GCI led to increased neurodegeneration and microglia/macrophage activation in the hippocampus, and increased IL-1β and KC protein expression in the hippocampus at 72 hours. Hypothermia therapy attenuated these inflammatory responses. It also improved spatial learning/memory at 7 and 21 days, and preserved contextual fear response 21 days post-ischemia. Hypothermia therapy attenuated the post-ischemic inflammatory response, protected hippocampal neurons, and preserved long-term memory and learning.

Previous research on the relationship between spatial memory and adult hippocampal neurogenesis has been controversial. In the present study, neurogenesis was compared between two natural populations of the same species that differ in their reliance on spatial memory to cache and retrieve stored food. Western red squirrels store food in a single site whereas eastern red squirrels store food in multiple sites. Neurogenesis was assessed using endogenous markers of the number of proliferating cells (Ki-67) and the number of immature neurons (DCX), and neuronal recruitment was determined by measuring the area of the dentate gyrus of the hippocampus. The number of proliferating cells, immature neurons and neuronal recruitment were enhanced in the eastern compared to the western red squirrels, reflecting the food storing strategies used by the squirrels. This suggests that there is a positive correlation between adult hippocampal neurogenesis and spatial learning and memory.

The aim of the present study was to examine retention of spatial reference memory after 6 (Experiment I) and 15days (Experiment II) of binge-like drinking and during alcohol withdrawal in young adult Wistar rats. Prior to alcohol treatment, rats received Morris Water Maze (MWM) training. Afterwards, rats were intragastrically administered ethanol at the dose increasing from 4.5g-to-12g/kg. Intubation control groups (n=7 and n=10, respectively) received infusions of a sucrose solution without ethanol. Subsequently, all subjects were given a single probe trial in the MWM to test memory retention. In both experiments, there were three alcohol groups: A0 group (n=7) tested 4h after the last alcohol administration for acute effects of ethanol / A24 group (n=7) tested 24h after alcohol cessation, when acute ethanol effects disappear but withdrawal symptoms does not develop yet / A72 group (n=7) tested 72h after the last ethanol infusion for withdrawal effects. Finally, potential molecular changes in hippocampus were examined using Fourier Transform Infra-Red (FT-IR) spectroscopy. The blood alcohol concentration was 605.67&plusmn / 36mg/dl. In Experiment I, due to the low overall level of performance in the memory retention task the behavioral effects of ethanol could not be evaluated and no significant between&ndash / group differences were observed in Experiment II. In Experiment I, no significant changes in the molecular make-up of the hippocampus were noted. Conversely, in Experiment II, significant changes in protein, lipid, and nucleic acid profiles related to ethanol intake and withdrawal were found. They are linked to both development of tolerance to ethanol and adverse withdrawal effects.

This study investigated spatial learning in Caenorabditis elegans; the ability to associate reinforcing cues with a location. Naive, wildtype C. elegans were trained in a microfluidic t-maze in the presence of diacetyl (a volatile attractant associated with food) and subsequently tested to see if they could associate diacetyl with one arm of the t-maze. 70-80% of the subjects chemotaxed towards diacetyl during training phase, but they randomly chose left or right when diacetyl was absent (number of subjects that chose diacetyl being under 65%). From our experiments, it is unlikely that the worms are associating diacetyl with one arm of the t-maze, but appears to be using some component of the atmosphere as a cue.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Decline cognitive related to neurodegenerative diseases are very commom in patients, probably in function of aging. Since there are few effectives therapeutics approaches to loss memory treatment, but studies about new therapeutics approaches are necessary regarding neuroprotective drugs. Thus, recent works have been showing the efficacy of some neuroprotective compounds like creatine (Cr) in treatment of patients and experimental models with memory defcit. Creatine is a guanidine compound synthesized from glycine, arginine and S-adenosylmethionine in the kidneys, liver and brain that have been presented neuroprotective and neuromodulatory effect in the central nervous systems. Some works suggest that guanidine compounds like Cr could enhance learning by modulation polyamines binding sites at the N-methyl-D-Aspartate (NMDA) receptor and act as energetic buffer intracellular. In these context, the propose of this work was investigate the involvement of Cr transporter (CreaT), cAMP-dependent protein kinase A (PKA) and Ca2+/ calmodulin-dependent protein kinase II (CaMKII) signaling pathway in the spatial learning after intrahippocampal injection of Cr. After training on Barnes Maze, Cr and/or 3-GPA (inhibitor CreaT), Cr and/or H-89 (PKA inhibitor), Cr and/or STO-609, (inhibitor of CaMKII) bilateral intrahipocappus administration was performed. The results showed that intrahippocampal administration of 3-GPA, H-89 and STO-609 attenuated the facilitatory effect of Cr on spatial learnig performed on barnes Maze. Therefore, we decide investigate the involvement of the PKA (pPKA), CaMKII (pCaMKII) and CREB (pCREB) activation after intrahippocampus creatine administration in rats trained on Barnes Maze. The results showed that Cr enhanced pCREB levels and pCaMKII levels. Thirty minutes after creatine administration was observed pCREB an pCaMKII levels enhancement, on the other hand, pPKA levels enhancement was not observed. These data suggest that spatial learning enhancement elicited by Cr may be mediated by trans-cellular creatine transports, as well, CaMKII/CREB intracellular pathway in rat hippocampus / O declínio cognitivo associado a doenças neurodegenerativas é um sintoma cada vez mais comum encontrado em pacientes, provavelmente devido ao aumento da expectativa de vida da população. Dada a escassez de medidas terapêuticas efetivas para o déficit de memória apresentado por pacientes, evidencia-se a importância da busca de novos compostos e do estudo de seus mecanismos de ação. Nesse contexto, recentes estudos mostraram a eficácia de algumas substâncias com ação neuroprotetora, como a creatina (Cr), na terapia de pacientes com déficit de memória e em modelos experimentais. A Cr é um composto guanidínico sintetizado endogenamente nos rins, fígado, pâncreas e cérebro, que apresenta ação neuroprotetora e neuromoduladora no sistema nervoso central. Estudos mostram que a administração de compostos guanidínicos, como a Cr, podem estar relacionados com a melhora da memória devido à interação com o sítio das poliaminas no receptor N-metil-D-Aspartato (NMDA) e por atuar como tampão energético intracelular. Neste contexto, o objetivo deste estudo foi investigar o envolvimento do transportador de Cr (CreaT), das proteínas quinases dependente de AMPc (PKA) e dependente de Ca2+/calmodulina II (CaMKII) na melhora do aprendizado espacial induzido por Cr no hipocampo de ratos. Após o treino no labirinto de Barnes, os ratos foram injetados no hipocampo, bilateralmente, com Cr e/ou 3-ácido guanidinico propiônico (3-GPA, um inibidor do transportador de creatina); Cr e/ou [N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide, Di-HCl Salt] (H-89, um inibidor da PKA); Cr e/ou 1,8-Naphthoylene benzimidazole-3- carboxylic acid (STO-609, um inibidor da CaMKII). A administração de 3-GPA, H-89 e STO-609 diminuiu o efeito facilitatório da Cr na memória espacial de ratos, observado no teste do labirinto de Barnes. De acordo com esses resultados, decidimos investigar o envolvimento da ativação do elemento de ligação responsivo ao AMPc (pCREB), PKA (pPKA) e CaMKII (pCaMKII) após a administração de Cr no hipocampo de animais treinados no labirinto de Barnes. Trinta minutos após a injeção de Cr, foi observado um aumento nos níveis de pCREB e pCaMKII, mas não nos níveis de pPKA no hipocampo de ratos. Estes achados sugerem que a facilitação do aprendizado espacial induzido pela Cr depende do seu transporte para o meio intracelular, assim como, envolve a via de sinalização celular da CaMKII/CREB no hipocampo de ratos.

Made available in DSpace on 2016-06-02T20:19:28Z (GMT). No. of bitstreams: 1 887.pdf: 469528 bytes, checksum: fc5bcdbae3a402aaac1aae4dbf59bcd1 (MD5) Previous issue date: 2006-03-03 / Universidade Federal de Sao Carlos / This work intended to investigate in forebrain ablated Carassius auratus the effect of the H1 receptor blockade in a spatial choice task using a T-maze test with positive reinforcement. Sixty-nine goldfish were submitted to surgery for removal of both telencephalic lobes five days before the beginning of the experiment. A T-shaped glass aquarium, which had two feeders located at the extremities of the long arm, was employed. One of the two feeders was blocked. The experimental trials were performed in nine consecutive days. Each fish was individually placed in the short arm and confined there for thirty seconds, then it was allowed to swim through the aquarium to search for the food for ten minutes (maximum period). Time to find food was analysed in seconds. Animals were injected intraperitoneally with chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial, ten minutes after it had been replaced at house aquarium. Data were analyzed via a three-way analysis of variance (ANOVA) with repeated measures, and post hoc comparisons were analyzed using the Student Newman-Keuls test (p<0.05). All the training latencies of A-SAL group were significantly higher than latencies of S-SAL group (p<0.05). S-SAL group showed a significative decrease in latencies at the second trial and maintained that reduction until the end of the experiment (p<0.05), S-CPA group demonstrated a decrease only after the fourth trial (p<0.01), A-SAL group showed reduced latencies after the fifth trial (p<0.05), and ACPA group did not showed any difference between training latencies. Thus, our results showed that CPA seems to impair the consolidation of memory either on telencephalon ablated animals and in sham-operated ones. Furthermore, this work supports evidence that histamine plays a facilitatory role in learning and memory processes of a spatial task through its action in primitive structures of the brain in teleost fish. / O objetivo deste trabalho foi investigar, em peixes da espécie Carassius auratus submetidos à ablação telencefálica, o efeito do bloqueio do receptor H1 em uma tarefa de escolha espacial utilizando um teste de labirinto em T com reforço positivo. Sessenta e nove peixes foram submetidos à cirurgia para a remoção de ambos os lobos telencefálicos cinco dias antes do início do experimento. Foi empregado um aquário de vidro transparente em forma de T, o qual teve dois comedouros fixados nas extremidades do braço longo, sendo que um dos comedouros foi bloqueado durante as sessões de treino. O experimento foi realizado em nove sessões consecutivas realizadas com intervalos de 24 horas. Individualmente, cada peixe foi confinado no compartimento de saída do aquário experimental durante trinta segundos, e então foi permitido a ele explorar todo o aquário para procurar o alimento durante dez minutos (período máximo). O tempo utilizado para encontrar o alimento foi cronometrado em segundos. Os animais foram injetados intraperitonealmente com clorfeniramina (CPA), na dose de 16 mg/kg de peso corporal, ou salina após cada treino, dez minutos após o peixe ter sido recolocado no aquário de manutenção. Os dados foram analisados através de ANOVA de três vias seguida pelo teste de comparações múltiplas de Student Newman-Keuls. Todas as latências de treino do grupo A-SAL foram significativamente maiores do que as do grupo LFSAL (p<0,05). O grupo LF-SAL demonstrou diminuição significativa das latências apartir do segundo dia de treino (p<0,05), o LF-CPA apresentou esta diminuição após o quarto dia de treino (p<0,01), o A-SAL apresentou redução após o quinto dia de treino (p<0,05), e não foram encontradas diferenças entre as latências no grupo A-CPA. Assim, nossos resultados mostraram que a CPA parece prejudicar a consolidação da memória tanto nos animais que tiveram o telencéfalo removido quanto nos que foram submetidos à lesão fictícia. Além disto, este trabalho dá suporte às evidências de que a histamina desempenha um papel facilitatório nos processos de aprendizagem e memória em uma tarefa de escolha espacial, atuando em estruturas primitivas do cérebro de teleósteos.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-10-11T14:19:54Z No. of bitstreams: 1 julianamaddalenadias.pdf: 3037661 bytes, checksum: 359fe67232968dc67c4bff014a4f6e2a (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-10-11T16:01:00Z (GMT) No. of bitstreams: 1 julianamaddalenadias.pdf: 3037661 bytes, checksum: 359fe67232968dc67c4bff014a4f6e2a (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-10-11T16:01:11Z (GMT) No. of bitstreams: 1 julianamaddalenadias.pdf: 3037661 bytes, checksum: 359fe67232968dc67c4bff014a4f6e2a (MD5) / Made available in DSpace on 2016-10-11T16:01:11Z (GMT). No. of bitstreams: 1 julianamaddalenadias.pdf: 3037661 bytes, checksum: 359fe67232968dc67c4bff014a4f6e2a (MD5) Previous issue date: 2010-05-14 / A temática da favela tem sido abordada no ensino de Geografia como um espaço de ausências, principalmente, de infraestrutura urbana. Existe um silenciamento da pluralidade presente entre os espaços e lugares de seus moradores, justamente, em uma disciplina que se coloca na busca por um olhar crítico na formação do cidadão. Todavia, o saber escolar não se configura como exclusiva mediação na construção da noção de favela pelos alunos. Neste sentido, se na cultura contemporânea são inúmeros os modos do sujeito tecer sua aprendizagem espacial, por que não investigar como as crianças percebem e concebem a ideia de favela? Ouvir os alunos para compreender aquilo que media suas experiências com o espaço favela proporciona uma reflexão acerca de uma temática que está posta a todos- na cidade, na TV, nas conversas- e, de modo espacial, suscita o debate em torno da formação de professores. Diante de muitas geografias e da pluralidade das favelas, esta pesquisa procurou com base na Geografia Humanista ouvir crianças a partir de seus desenhos para conhecer como esses atores sociais percebem os sentidos das favelas. / The issue of slums has been addressed in the teaching of geography as an area of absences, especially in urban infrastructure. There is a silencing of the plurality present between the spaces and places for its residents, just in a discipline that arises in the search for a critical look at the individual development. However, the school does not know how to setup exclusive mediation in the construction of the concept of slum students. In this sense, if in contemporary culture there are many ways to weave their learning of the subject space, why not investigate how children perceive and conceive the idea of slum? Listening to the students to understand what media their experiences with the slum area provides a reflection on a theme that is called the all-in town, on TV, in conversations, and, in space, raises the debate on the formation of teachers. Before many geographies and the plurality of slums, this research sought based on the Humanist Geography hear children from their drawings to know how they perceive the social meanings of the slums.

Animals must sense their surroundings to update their internal representations of the external environment, and exploratory behaviours such as sensory sampling are influenced by past experiences. This thesis investigates how voluntary sensory sampling activities undergo learning-dependent changes. Studies of freely behaving animals impose two major challenges: 1) the accuracy of biological measurements is compromised by movement-induced artifacts, and 2) large degrees of freedom in unrestrained behaviours confound well-controlled studies. Pulse-type weakly electric fish (WEF) are an ideal choice to study adaptive sensory sampling from unrestrained animals, since they generate readily observable and quantifiable sensory capture events expressed by discrete pulses of electric organ discharges (EODs). To study the voluntarily movements and sensory sampling while animals navigated in darkness, we developed three novel experimental techniques to track movements and detect sensory sampling from a freely behaving WEF: 1) an EOD detector to remotely and accurately measure the sensory sampling rate, 2) an electrical tracking method to track multiple WEF using their own EODs, and 3) visual tracking algorithm for robust body tracking through water under infrared illumination. These techniques were successfully applied to reveal novel sensory sampling behaviours in freely exploring Gymnotus sp. Cortical activity precedes self-initiated movements by several seconds in mammals; this observation has led into inquiries on the nature of volition. Here we demonstrate the sensory sampling enhancement also precedes self-initiated movement by a few seconds in Gymnotus sp. Next, we tested whether these animals can be trained to learn a location of food using electrically detectable landmarks and, if so, whether they can use their past experiences to optimize their sensory sampling. We found that animals revisited the missing food location with high spatial accuracy, and they intensified their sensory sampling near the expected food location by increasing the number of EOD pulses per unit distance travelled.