Les connaissances actuelles de la physiopathologie de la migraine ne permettent pas encore de déterminer avec exactitude le processus pathologique à lorigine de lactivation du système trigémino-vasculaire conduisant à la céphalée migraineuse. Certains arguments sont en faveur danomalies fonctionnelles du cortex cérébral à même denclencher le processus de la crise de migraine. Parmi ces anomalies, une hypersensibilité sensorielle a été décrite de longue date et a conduit à un important travail en neurophysiologie clinique. Ainsi lutilisation des techniques de potentiels évoqués a abouti à divers résultats dont le plus reproductible consiste en un déficit dhabituation des réponses évoquées corticales lors de stimulations sensorielles répétées chez les migraineux en période intercritique. Comprendre lorigine du déficit dhabituation retrouvé chez les migraineux devrait permettre de préciser le rôle du cortex cérébral dans la cascade dactivation menant à la crise de migraine. Nous avons utilisé la stimulation magnétique transcrânienne répétitive (SMTr) chez les migraineux afin de moduler lexcitabilité des cortex visuel et moteur, en enregistrant ses effets respectivement sur les potentiels évoqués visuels et moteurs. La SMTr a ainsi permis détudier lorigine du déficit dhabituation des potentiels évoqués corticaux retrouvé en période intercritique chez les migraineux. Ce déficit dhabituation des réponses corticales semble provenir dun niveau réduit de préactivation corticale mais également dune activité réduite des interneurones inhibiteurs corticaux. Par ailleurs, ce déficit dhabituation ne semble pas être un élément pathogénique prépondérant dans la mesure où sa seule présence chez les sujets sains ne permet pas den faire des migraineux. Il pourrait correspondre soit à un épiphénomène, soit à un des éléments étiopathogéniques de la migraine, au même titre que la prédisposition génétique, les troubles du métabolisme mitochondrial, Il est vraisemblable que le poids relatif de chacun de ces éléments étiopathogéniques participe à lhétérogénéité des migraines.

Bibliografická identifikace v angličtině Author's first name and surname: Lenka Boťchová, BA Title of the master thesis: Does status epilepticus during early postnatal period influence laboratory rat psychomotor development? Department: Department of Rehabilitation and Exercise Medicine Supervisor: doc. PharmDr. H. Kubová, DrSc. The year of presentation: 2013 Abstract: The purpose of this study is to evaluate the influence of status epilepticus (SE) in postnatal development early phase on laboratory rat psychomotor development. Experimentally caused (SE) is the most common mode of epileptogenesis, which is the process leading to the epilepsy creation, and typical comorbidities. The influence of the early SE was studied when using lithium/pilocarpine model of SE induced on 12 days old rat cubs, which were repeatedly exposed to the "open field" test until 32nd day of their lives that means until the puberty beginning. The evaluation is focused on cognition and overall locomotion changes and anxiety demonstrations. The results show that in short periods after SE (up to 1 month) the cognitive functions regarding the habituation disorder are not worsened. However, hyperactivity short-term disposition and worse adaptability to experimental conditions due to animal anxiety increase were detected. Motor skills of...

Neste estudo foram avaliados os efeitos de restrições biomecânicas e de carga sobre a adaptação de respostas posturais automáticas (RPAs) a perturbações externas não-antecipadas. No Experimento 1 o objetivo foi avaliar o efeito do ângulo de orientação dos pés em RPAs causadas por perturbações de diferentes magnitudes. A perturbação foi gerada a partir da liberação inesperada de carga presa ao tronco do participante, levando à oscilação anterior do corpo. Foram avaliadas RPAs para cargas correspondendo a 5% e 10% do peso corporal do participante, comparando as seguintes orientações dos pés: paralelos, preferida (M = 10,46°), 15° e 30° para cada pé a partir da linha média do corpo. Os resultados mostraram que a perturbação com a carga 10% levou a maiores deslocamentos do centro de pressão e rotação das articulações, além de respostas musculares mais fortes e mais rápidas. Os pés orientados em 30° levaram ao maior deslocamento do centro de pressão em comparação com as outras angulações. A perturbação com a carga 5% levou a respostas similares para ambas as articulações, enquanto que com a carga 10% a amplitude de rotação das articulações foi maior com pés orientados em 30°. No Experimento 2, os objetivos foram avaliar o efeito de tentativas prévias com carga distinta, e a adaptação das respostas posturais em tentativas repetidas com mesma carga, em RPAs a uma perturbação não-antecipada. Foram empregadas três cargas para perturbação: 6%, 8% e 10% do peso corporal do participante. Este experimento foi realizado por meio da comparação de dois grupos: sequência alta-baixa, para o qual a ordem de aplicação das cargas se dava de forma decrescente; e sequência baixa-alta, para o qual a ordem de aplicação das cargas se dava de forma crescente. Os resultados mostraram que as respostas posturais foram graduadas de acordo com a magnitude da carga. O efeito de sequência de cargas foi observado na maior amplitude de deslocamento do centro de pressão para o grupo decrescente em relação ao crescente. A análise do centro de massa indicou adaptação intertentativas, com redução progressiva da amplitude de deslocamento entre a primeira e a última tentativa na carga de 10%. Esses resultados sugerem que respostas posturais reativas são produzidas levando em consideração não apenas feedback sensorial, mas também respostas posturais precedentes. Em uma análise global, os resultados deste estudo revelam a sensibilidade do sistema de controle postural a fatores contextuais, incluindo restrições biomecânicas e respostas a perturbações prévias, na geração de respostas posturais automáticas a uma perturbação da estabilidade do equilíbrio corporal / In this study we evaluated the effects of biomechanical constraints and load on the adaptation of automatic postural responses (APRs) to external perturbations of different magnitudes. The objective of Experiment 1 was to evaluate the effect of feet orientation angle in APRs caused by perturbations of different magnitudes. The perturbation was generated through unexpected load release attached to the participant\'s trunk, leading to forward body sway. APRs were evaluated for loads corresponding to 5% and 10% of participant\'s body weight, comparing the following feet orientations: parallel, preferred (M = 10.46°), 15° and 30° for each foot regarding the body midline. Results showed that APRs were sensitive to perturbation magnitude, with 10% load leading to higher center of pressure displacement and amplitude of leg joints rotation, in addition to stronger and faster muscle responses. Feet oriented at 30° led to higher center of pressure displacement compared to other angles. The 5% load led to similar responses for both the hip and ankle joints in the different orientations, while for the 10% load amplitude of legs joints rotation was higher for the feet oriented at 30° in comparison with the other orientation angles. In Experiment 2, we evaluate the effects of previous responses to a different perturbation load, and adaptation to the same load over repeated perturbations, on APRs to unanticipated perturbations. Three perturbation loads were employed: 6%, 8% and 10% of participant\'s body weight. The experiment was performed by comparing two groups: high-low sequence, with decreasing sequence of loads; and low-high sequence, with increasing sequence of loads. Results showed that postural responses were scaled according to load magnitude. The decreasing loads sequence led to higher amplitudes of center of pressure displacement in comparison to the increasing sequence. Analysis of center of mass indicated intertrials adaptation, with progressive reduction of amplitude displacement between the first and last trial in the 10% load. These results suggest that reactive postural responses are produced taking into consideration not only sensory feedback but also previous postural responses. Overall, results from this study reveal the sensitivity of the postural control system to contextual factors, including biomechanical constraints and responses to previous perturbations, in the generation of automatic postural responses to an unanticipated perturbation of balance stability.

O envelhecimento torna a memória particularmente vulnerável e em roedores, induz déficits no desempenho de tarefas que envolvem memória espacial e operacional. Além disso, o envelhecimento está associado a uma diminuição dos comportamentos exploratórios e com aumento na linha de base da ansiedade. Estratégias que visem à prevenção dos transtornos de ansiedade e deficiências cognitivas proporcionando a melhoria da qualidade de vida de idosos são de grande valia. O treinamento cognitivo previne processos de neurodegeneração e perdas da função hipocampal, promovendo uma melhora no desempenho de habilidades cognitivas. Porém, pouco se sabe como o treino em uma tarefa específica afeta outros aspectos cognitivos e emocionais. Para testar os efeitos do treinamento em uma tarefa de memória operacional espacial na ansiedade, habituação e na densidade de células no hipocampo de ratos foram utilizados quatro grupos de animais. Ratos idosos e jovens treinados na tarefa de memória operacional (dependente do hipocampo) e idosos e jovens treinados em uma tarefa com pista visível (independente do hipocampo) no labirinto aquático de Morris (LAM). Após o término dos treinos os animais foram exposto ao teste e re−teste no labirinto em cruz elevado (LCE) e ao teste em campo aberto (TCA). Outros animais após os treinos foram perfundidos e os hipocampos foram processados em coloração de Nissl para quantificação da densidade de células no hipocampo. Ocorreu um prejuízo na aquisição no LAM, nos animais idosos submetidos à tarefa de memória operacional e na tarefa com a pista visível, porém com o decorrer das sessões em ambas as tarefas os animais idosos apresentam níveis de desempenho semelhantes a dos jovens. O treinamento cognitivo em memória operacional espacial resulta em efeitos significativos sobre a diminuição de comportamentos similares a ansiedade no LCE e a altera taxa de habituação no TCA em ratos idosos comparado aos animais idosos expostos a tarefa com a pista visível, entretanto não altera a densidade de células no hipocampo entre grupos jovens e idosos e entre os diferentes treinamentos. O treinamento cognitivo em memória operacional no LAM tem efeitos significativos sobre níveis de ansiedade e taxa de habituação em animais idosos e parece ser uma tarefa promissora para investigações a natureza das modificações plásticas neurais resultantes do treinamento. / Decline in memory fuctions are related to aging process. Spatial learning and memory deficits are induced by aging in rodents. Elderly also correlates with decreases in exploratory behaviour and increments in baseline anxiety. The development of strategies that focus on the prevention of anxiety disorders and cognitive disabilities are needed to improve the welfare. Cognitive training prevents neurodegeneration processes and loss of hippocampal function, and provides improvements on performance of cognitive skills. However, remains unclear how training on a specific task affects another cognitive and emotional aspects. To evaluate the effects of training on spatial working memory task on anxiety, habituation and cell density in the hippocampus, we used aged and young rats trained in the working memory task (dependent of the hippocampus) or in a task with visible track (independent of the hippocampus) in the Morris water maze (MWM). After MWM training clousure the animals were exposed to the test and re−test in the elevated plus maze and the open field test. Subsenquently to behavioural tests animals were perfused and the hippocampus was processed for Nissl staining to quantify the density of hippocampal cells. The acquisition of the MWM task was disrrupted in aged animals submitted to working memory task and visible platform task, however the aged animals were capable to learn the task during the training and exhibit similar performance to youngest. Cognitive training on spatial working memory leads to reduction of anxiety-like behaviours in the elevated plus maze and modify habituation rate in the open field in aged rats compared to animals that were exposed to visible task. Although no differences were found in the hippocampus cell density between young and aged rats and also for different training. Cognitive training on the working memory version of MWM leads to decrease of anxiety levels and habituation rate in aged animals and could be an important tool to investigate plastic neural changes induced by training.

Neste estudo foram avaliados os efeitos de restrições biomecânicas e de carga sobre a adaptação de respostas posturais automáticas (RPAs) a perturbações externas não-antecipadas. No Experimento 1 o objetivo foi avaliar o efeito do ângulo de orientação dos pés em RPAs causadas por perturbações de diferentes magnitudes. A perturbação foi gerada a partir da liberação inesperada de carga presa ao tronco do participante, levando à oscilação anterior do corpo. Foram avaliadas RPAs para cargas correspondendo a 5% e 10% do peso corporal do participante, comparando as seguintes orientações dos pés: paralelos, preferida (M = 10,46°), 15° e 30° para cada pé a partir da linha média do corpo. Os resultados mostraram que a perturbação com a carga 10% levou a maiores deslocamentos do centro de pressão e rotação das articulações, além de respostas musculares mais fortes e mais rápidas. Os pés orientados em 30° levaram ao maior deslocamento do centro de pressão em comparação com as outras angulações. A perturbação com a carga 5% levou a respostas similares para ambas as articulações, enquanto que com a carga 10% a amplitude de rotação das articulações foi maior com pés orientados em 30°. No Experimento 2, os objetivos foram avaliar o efeito de tentativas prévias com carga distinta, e a adaptação das respostas posturais em tentativas repetidas com mesma carga, em RPAs a uma perturbação não-antecipada. Foram empregadas três cargas para perturbação: 6%, 8% e 10% do peso corporal do participante. Este experimento foi realizado por meio da comparação de dois grupos: sequência alta-baixa, para o qual a ordem de aplicação das cargas se dava de forma decrescente; e sequência baixa-alta, para o qual a ordem de aplicação das cargas se dava de forma crescente. Os resultados mostraram que as respostas posturais foram graduadas de acordo com a magnitude da carga. O efeito de sequência de cargas foi observado na maior amplitude de deslocamento do centro de pressão para o grupo decrescente em relação ao crescente. A análise do centro de massa indicou adaptação intertentativas, com redução progressiva da amplitude de deslocamento entre a primeira e a última tentativa na carga de 10%. Esses resultados sugerem que respostas posturais reativas são produzidas levando em consideração não apenas feedback sensorial, mas também respostas posturais precedentes. Em uma análise global, os resultados deste estudo revelam a sensibilidade do sistema de controle postural a fatores contextuais, incluindo restrições biomecânicas e respostas a perturbações prévias, na geração de respostas posturais automáticas a uma perturbação da estabilidade do equilíbrio corporal / In this study we evaluated the effects of biomechanical constraints and load on the adaptation of automatic postural responses (APRs) to external perturbations of different magnitudes. The objective of Experiment 1 was to evaluate the effect of feet orientation angle in APRs caused by perturbations of different magnitudes. The perturbation was generated through unexpected load release attached to the participant\'s trunk, leading to forward body sway. APRs were evaluated for loads corresponding to 5% and 10% of participant\'s body weight, comparing the following feet orientations: parallel, preferred (M = 10.46°), 15° and 30° for each foot regarding the body midline. Results showed that APRs were sensitive to perturbation magnitude, with 10% load leading to higher center of pressure displacement and amplitude of leg joints rotation, in addition to stronger and faster muscle responses. Feet oriented at 30° led to higher center of pressure displacement compared to other angles. The 5% load led to similar responses for both the hip and ankle joints in the different orientations, while for the 10% load amplitude of legs joints rotation was higher for the feet oriented at 30° in comparison with the other orientation angles. In Experiment 2, we evaluate the effects of previous responses to a different perturbation load, and adaptation to the same load over repeated perturbations, on APRs to unanticipated perturbations. Three perturbation loads were employed: 6%, 8% and 10% of participant\'s body weight. The experiment was performed by comparing two groups: high-low sequence, with decreasing sequence of loads; and low-high sequence, with increasing sequence of loads. Results showed that postural responses were scaled according to load magnitude. The decreasing loads sequence led to higher amplitudes of center of pressure displacement in comparison to the increasing sequence. Analysis of center of mass indicated intertrials adaptation, with progressive reduction of amplitude displacement between the first and last trial in the 10% load. These results suggest that reactive postural responses are produced taking into consideration not only sensory feedback but also previous postural responses. Overall, results from this study reveal the sensitivity of the postural control system to contextual factors, including biomechanical constraints and responses to previous perturbations, in the generation of automatic postural responses to an unanticipated perturbation of balance stability.

An interesting paradox in the developmental literature has emerged in which fast-habituating babies tend to be temperamentally difficult and fast language learners, even though temperamentally difficult babies tend to be slow language learners. The purpose of the present investigation was to examine whether the paradoxical relationships among habituation, temperamental difficulty, and language acquisition could be mediated partly or wholly by infant attentional focus, because the latter also tends to correlate with temperamental difficulty and vocabulary size. Forty mother–infant dyads were followed from child age 5–20-months. Results replicated those of Tamis-LeMonda and Bornstein (Child Develop 1989, 60, 738–751): measures of visual habituation at 5 months were related to 13-month vocabulary. However, relationships between 5-month habituation and 20-month vocabulary were moderated by temperamental attentional focus. For children low in attentional focus, 5-month habituation was related negatively to 20-month productive vocabulary; whereas for children high in attentional focus, early habituation was positively related to later vocabulary. Results are consistent with a model of habituation in which volitional attentional focus overrides basic attentional mechanisms that occur during habituation.

The phenomenon of attentional bias to alcohol, where drinkers demonstrate a preference in allocating visual attention towards alcohol-related stimuli rather than neutral stimuli, is well-established. Studies detecting this phenomenon typically utilize computer-administered stimulus presentation tasks such as the visual dot probe task. Despite their frequency of use, these tasks do not represent the ways in which individuals typically encounter alcohol outside of the laboratory. Typical environments where alcohol is present allow individuals to move about freely and encounter alcohol while also being exposed to many other stimuli. This dissertation sought to implement a novel approach to assessing attentional bias in vivo, and identify how alcohol consumption might influence such in vivo attentional bias. This two-study dissertation utilized an in vivo task where participants looked freely around a room representing a recreational setting containing numerous objects while portable eye-tracking glasses monitored what an individual looked at and for how long. Target items of alcohol and neutral beverages were placed throughout the environment and fixation time spent on these objects was recorded. The first study of this dissertation examined attentional bias to alcohol-related objects across two identical testing sessions to understand the impact of novelty on allocation of in vivo attention. The second study tested individuals using the same in vivo assessment following a 0.30 g/kg dose of alcohol, a 0.65 g/kg dose of alcohol and a placebo. Participants also completed the visual dot probe task in order to measure and compare their attentional bias in a more traditionally implemented task to the novel in vivo approach. Results from the first study indicate that as the novelty of stimuli begins to wane and habituation to neutral stimuli occurs, attentional bias to alcohol-related objects emerges. This attentional bias was shown to be related to drinking habits, where heavier drinkers demonstrated increased attentional bias. The second study in this research found no discernible effect of alcohol consumption on in vivo attentional bias, but did identify a satiating effect of consumption on bias as measured by the visual dot probe task. Additional visual dot probe findings suggest the specificity of the effect of alcohol consumption on attentional bias. Together, these findings help inform whether there is benefit in utilizing an ecological model of measuring attentional bias and how the phenomenon might be measured in laboratory settings in the future.

It has been proposed that the various 14-3-3 isotypes and isoforms present in all eukaryotes are largely functionally equivalent. However, this is not consistent with the conservation of multiple isoforms and isotypes, especially in vertebrates with seven 14-3-3 encoding genes and nine isotypes. The hypothesis tested in this thesis is that both isoform-specific and overlapping functions are likely mediated through tissue specific expression, colocalization and dimerization of 14-3-3 proteins occur in vivo. Drosophila melanogaster was selected because it offers a simple, but representative system to study these proteins functionally. This thesis focuses primarily on D14-3-3?, although the expression pattern and phenotypes associated with all three Drosophila 14-3-3s were determined. I first determined the expression pattern of the three different 14-3-3 isotypes (leoI, leoII and D14-3-3?) and described developmental phenotypes associated with mutations in 14-3-3 isotypes in Drosophila. I found that there is partial redundancy with respect to lethality. Both LEO and D14-3-3? appear required for normal germ-line and somatic gonadal development. However, they do not appear to be functionally equivalent with respect to this phenotype since LEO is unable to compensate for the loss of D14-3-3?. I also determined that D14-3-3? mutants have unique phenotypes including deficits in adult cross-vein formation and rapid habituation to olfactory and footshock stimuli. To further understand the unique role that D14-3-3? plays in the adult CNS, I mapped the areas in the brain involved in olfactory and footshock habituation. I found that although the mushroom bodies (MBs) are necessary to inhibit premature habituation such as that exhibited by D14-3-3? mutants, D14-3-3? expression specifically in the MBs is not sufficient to rescue premature habituation. Although the loss of either LEO or D14-3-3? appears to cause a deficit in olfactory associative learning, premature habituation is the cause of the deficit seen in D14-3-3? mutants. As leo mutants do not exhibit a premature habituation phenotype, it appears that within the MBs LEO and D14-3-3? are not functionally equivalent. Therefore, the data supports the hypothesis that 14-3-3s have functional specificity and redundancy likely to represent use of homo and heterodimers in different processes within the tissues of an organism.

In Syrian hamsters, sexual preference requires integration of chemosensory and steroid cues. Although data suggest that separate pathways within the brain process these two signals, the functional significance of this separation is not well understood. Within the medial amygdala, the anterior region (MEa) receives input from the olfactory bulbs, whereas the posterodorsal region (MEpd) is sensitive to steroid hormones. Lesions of either the MEa or MEpd eliminated preference to investigate female over male odors. Importantly, males with MEpd lesions displayed decreased attraction toward female odors, suggesting a decrease in sexual motivation. In contrast, males with MEa lesions displayed high levels of investigation of both female and male odors, suggesting an inability to categorize the relevance of the odor stimuli. These results suggest that both the MEa and MEpd are critical for the expression of opposite-sex odor preference, although they appear to mediate distinct aspects of this behavior.

It has been proposed that the various 14-3-3 isotypes and isoforms present in all eukaryotes are largely functionally equivalent. However, this is not consistent with the conservation of multiple isoforms and isotypes, especially in vertebrates with seven 14-3-3 encoding genes and nine isotypes. The hypothesis tested in this thesis is that both isoform-specific and overlapping functions are likely mediated through tissue specific expression, colocalization and dimerization of 14-3-3 proteins occur in vivo. Drosophila melanogaster was selected because it offers a simple, but representative system to study these proteins functionally. This thesis focuses primarily on D14-3-3?, although the expression pattern and phenotypes associated with all three Drosophila 14-3-3s were determined. I first determined the expression pattern of the three different 14-3-3 isotypes (leoI, leoII and D14-3-3?) and described developmental phenotypes associated with mutations in 14-3-3 isotypes in Drosophila. I found that there is partial redundancy with respect to lethality. Both LEO and D14-3-3? appear required for normal germ-line and somatic gonadal development. However, they do not appear to be functionally equivalent with respect to this phenotype since LEO is unable to compensate for the loss of D14-3-3?. I also determined that D14-3-3? mutants have unique phenotypes including deficits in adult cross-vein formation and rapid habituation to olfactory and footshock stimuli. To further understand the unique role that D14-3-3? plays in the adult CNS, I mapped the areas in the brain involved in olfactory and footshock habituation. I found that although the mushroom bodies (MBs) are necessary to inhibit premature habituation such as that exhibited by D14-3-3? mutants, D14-3-3? expression specifically in the MBs is not sufficient to rescue premature habituation. Although the loss of either LEO or D14-3-3? appears to cause a deficit in olfactory associative learning, premature habituation is the cause of the deficit seen in D14-3-3? mutants. As leo mutants do not exhibit a premature habituation phenotype, it appears that within the MBs LEO and D14-3-3? are not functionally equivalent. Therefore, the data supports the hypothesis that 14-3-3s have functional specificity and redundancy likely to represent use of homo and heterodimers in different processes within the tissues of an organism.