De nombreuses études expérimentales montrent que les canaux calciques activés par la dépolarisation membranaire, tout particulièrement les canaux calciques de type T (canaux T), jouent un rôle important dans la physiopathologie des épilepsies. Il existe trois isoformes des canaux T, Cav3.1, Cav3.2 et Cav3.3, toutes exprimées au niveau neuronal. De manière classique, c'est dans l'épilepsie absence où les canaux T ont été le plus étudiés. Les canaux T jouent également un rôle dans des modèles d'épilepsie partielle secondairement généralisée, comme le modèle pilocarpine qui mime l'épilepsie du lobe temporal (ELT). Jusqu'à présent ces canaux ne possédaient pas de pharmacologie spécifique, mais plusieurs molécules récemment synthétisées, en particulier le TTA-A2, apparaissent sélectives des canaux T. Le premier objectif de ma thèse était d'étudier l'implication des canaux T dans l'épileptogenèse. Pour cela nous avons traité des souris au TTA-A2 pendant la phase de latence du modèle pilocarpine (modèle ELT). Nos conditions expérimentales ne nous ont pas permis de conclure quant à une action protectrice du TTA-A2 dans ce modèle. Le deuxième objectif était d'étudier l'effet du TTA-A2 sur des modèles murins de convulsions généralisées : le modèle du Maximal Electroshock Seizure (MES) et le modèle pentylènetétrazole (PTZ). Deux lignées de souris inactivées pour les isoformes Cav3.1 ou Cav3.2 (KO Cav3.1 et KO Cav3.2) ont également été caractérisées dans cette étude. Nous montrons que le TTA-A2 réduit l'apparition des crises toniques dans le modèle MES et que les souris KO Cav3.1 sont également protégées, suggérant un rôle prépondérant des canaux Cav3.1 dans le développement des crises toniques. / Numerous experimental studies show that calcium channels activated by membrane depolarization, especially T-type calcium channels (T-channels), play an important role in the physiopathology of epilepsy. There are three T-channels isoforms, Cav3.1, Cav3.2 and Cav3.3, all expressed in neuronal level. Conventionally, T-channels were the most studied in absence epilepsy. T-channels are also involved in partial secondarily generalized epilepsy models, as the pilocarpine model that mimics temporal lobe epilepsy (TLE).Up to now, there was no specific pharmacology for this channels, but several molecules have recently been synthesized, particularly TTA-A2, appearing selective T-channels. The first goal of my thesis was to study the T-channels involvement in epileptogenesis. For this purpose we treated mice with TTA-A2 during the silent phase of the pilocarpine model (TLE model). Our experimental conditions do not allow us to conclude about a possible protective action of TTA-A2 on this model. The second goal was to study TTA-A2 effects on mice models of generalized seizures: the Maximal Electroshock model (MES) and the pentylenetetrazole model (PTZ). Two mice strains knock-out for Cav3.1 or Cav3.2 (KO Cav3.1 and KO Cav3.2) have also been characterized in this study. We show that the TTA-A2 reduces the appearance of tonic seizures in the MES model and the KO Cav3.1 mice are also protected, suggesting a preponderant role of Cav3.1 channels in the development of tonic seizures.

L’objectif de ce travail a été d’analyser les effets d’une préparation motrice sur l’activité des motoneurones (MN). Pour cela, des protocoles expérimentaux combinant l’enregistrement unitaire de l’activité des unités motrices des muscles extenseurs du poignet avec des paradigmes de préparation motrice de nature temporelle ont été utilisés chez l’Homme. L’analyse des caractéristiques de la décharge tonique des MN montre un allongement des intervalles inter-potentiels associé à une diminution de leur variabilité durant la période préparatoire, bien avant que la réponse motrice ne soit déclenchée. Ces changements démontrent clairement l’implication de mécanismes inhibiteurs spinaux au cours de la préparation motrice pouvant s’exercer au travers d’interneurones prémotoneuronaux. Il est montré que les modulations d’activité motoneuronales induites par la préparation motrice ne sont ni spécifiques au muscle effecteur de la réponse motrice ni prédictifs de la performance. Il est proposé que l’inhibition exercée sur les MN pendant la préparation motrice constitue un mécanisme généralisé de frein pour retenir le déclenchement prématuré de la réponse motrice, tandis que la diminution de variabilité dans la décharge serait un phénomène de compensation, permettant de produire des forces stables malgré la désactivation motoneuronale. L’implication du niveau motoneuronal dans la préparation motrice montre qu’une information au préalable influence l’état du système moteur jusqu’à son élément le plus périphérique, supportant ainsi le caractère hautement distribué des processus préparatoires. Ce travail a également conduit à proposer l’utilisation de l’entropie approximative pour l’analyse de l’activité motoneuronale, permettant d’éviter les écueils liés aux méthodes classiques d’analyse tout en respectant l’hypothèse d’un codage neuronal temporel. / The aim of this work was to analyze the effects of motor preparation on motoneuron (MN) activity. For this purpose, recordings of wrist extensor muscles motor unit activity were combined with time motor preparation paradigms in Human. Changes in the MN tonic discharge were found to occur during preparatory period, i.e. well before it is time to act. These changes were a lengthening of the mean inter-spike interval associated with a decrease of its variability. These data clearly demonstrate that spinal inhibitory mechanisms are activated during motor preparation and suggest the involvement of premotoneuronal interneurons. The modulations of motoneuronal activity induced by the motor preparation are neither specific to the agonist muscle involved in the motor response nor predictive of the performance. It is assumed that the inhibition acting on the MN during the motor preparation constitutes a general braking mechanism serving to prevent premature motor response, whereas the decrease of discharge variability would be a compensatory phenomenon, allowing to produce an efficient steady force in spite of lower motoneuronal activation. The involvement of the motoneuronal level in motor preparation demonstrates that advance information may influence the state of the motor system, including even the most peripheral motor neurons in the spinal cord, which supports the idea that motor preparation involves highly distributed functional processes. In addition, this work led us to argue in favor of the approximate entropy analysis as a suitable method for analyzing spike trains, allowing to detect changes in the regularity of the time-ordered inter-spikes intervals.

Gustav Mahler's Seventh Symphony seems to belie traditional notions of symphonic unity in that it progresses from E minor in the first movement to C major in the Finale. The repertoire of eighteenth and nineteenth century composers such as Haydn, Beethoven, and Brahms indicates that tonal holism is a significant factor for the symphonic genre. In order to reconcile Mahler's adventurous key scheme, this dissertation explores a multidimensional harmonic model that expands upon other concepts like Robert Bailey's double-tonic complex and transformation theory. A multidimensional musical object is a nexus of several interconnected chords that occupy the same functional space (tonic, dominant, or subdominant) and can be integrated into a Schenkerian reading. Mahler's Seventh is governed by a three-dimensional tonic object that encompasses the major and minor versions of C, E, and A-flat and the augmented triad that is formed between them. The nature of this multidimensional harmony allows unusual formal procedures to unfold, most notably in the first movement's sonata form. To navigate this particular sonata design, I have incorporated my own analytical terminology, the identity narrative, to track the background harmonic events. The location of these events (identity schism, identity crisis, and identity reclamation) is critical to the entire structure of the Seventh.

A leading theory for why we sleep focuses on memory consolidation - the process of stabilizing and strengthening newly acquired memories into long-term storage. Consolidation of memory for cognitive strategies and problem-solving skills is enhanced as compared to a period of daytime wakefulness. Importantly, sleep preferentially enhances memory for the cognitive strategy per se, over-and-above the motor skills that are used to execute the strategy. Although it has been known for some time that sleep benefits this type of memory, it is not known how this process unfolds during sleep, or how sleep transforms this memory trace in the brain. Sleep is classified into rapid eye movement (REM) sleep and non-REM (NREM) sleep. The role of REM sleep for consolidation of memory for problem-solving skills remains controversial. In addition, little attention has been paid to the possible distinct roles of phasic REM sleep (i.e., when bursts of eye movements occur) and tonic REM sleep (i.e., the presence of isolated eye movements and the absence of eye movement bursts). REM sleep might favour procedural memory consolidation for cognitive strategies and problem-solving skills, and the specific role of REM sleep in this process might be discernible only by differentiating between phasic and tonic REM states. In addition, fMRI studies have revealed that sleep-related consolidation of the memory trace for simple motor procedural skills is associated with strengthened activity of, and functional connectivity between, key memory-related brain areas (i.e., hippocampal, striatal, and neocortex). However, fMRI techniques have not yet been employed to investigate sleep-related consolidation of procedural memory for cognitive strategies and problem-solving skills. Participants (n=60) performed a procedural memory task involving a cognitive strategy while undergoing functional magnetic resonance imaging (fMRI) before and after a condition of Sleep, Nap, or Wake. Those in the Sleep and Nap condition underwent polysomnography (PSG) to further study the learning-related changes in sleep macrostructure and microstructure. This thesis not only shows that a period of sleep or a nap afford a greater benefit to memory consolidation of a procedural strategy than a period of wake, but more specifically: In Study 1, during sleep, phasic REM sleep theta power was directly associated with overnight improvement on the task, whereas tonic REM sleep sensorimotor rhythm power was greater following a night of learning compared to a non-learning control night. In Study 2, we show that distinct hippocampal, striatal, and cortical areas associated with strategy learning are preferentially enhanced. Study 3 reveals that the functional communication among these brain areas is greater following sleep compared to a daytime nap or day of wakefulness. Sleep-related changes in brain activation and functional connectivity were both correlated with improved performance from before to after a period of sleep. Overall, findings from this thesis support the benefit of sleep at the behavioural and systems level for consolidating procedural memory involving cognitive strategies used to solve problems. The findings suggest that the multifaceted nature of REM sleep must be examined separately by its phasic and tonic states, to identify the active role of REM sleep for consolidating memory. Further, the consolidation of the memory trace is reflected through activation of, and communication between hippocampal, striatal, and neocortical brain areas. In summary, this thesis shows that sleep actively consolidates memory for cognitive strategies and problem-solving skills.

L’ajustement de la pression expiratoire positive (PEP) durant la ventilation est difficile faute de cibles objectives. Cet enjeu est important en pédiatrie, car les nourrissons sont à risque de dérecrutement alvéolaire du fait de la faible rigidité de leur cage thoracique. Pour prévenir cela, ils maintiennent activement leurs volumes pulmonaires en conservant une activité tonique diaphragmatique (Edi tonique) durant l’expiration. La détection d’une Edi tonique élevée est donc un outil potentiel pour titrer la PEP. L’étude présentée dans ce mémoire a permis de proposer une première définition de l’Edi tonique élevée aux soins intensifs pédiatriques, soit > 3,2 mcV chez les 0-1 an et > 1,9 mcV chez les 1-18ans. Cette définition permettra d’aider à identifier au chevet les patients effectuant des efforts de recrutement et ainsi de pouvoir réévaluer le niveau optimal de PEP. Nous avons également montré que des épisodes d’Edi tonique élevée surviennent chez 62% des patients en ventilation non-invasive et 31% des patients intubés. Ces épisodes sont associés avec la bronchiolite, la tachypnée, et, chez les patients en ventilation non-invasive, à une hypoxémie plus sévère. La majorité des patients ayant présenté des épisodes n’avaient pas de contreindications à l’augmentation de la PEP. Ceci porte à croire qu’une stratégie d’ajustement neural continu de la PEP pourrait être une avenue intéressante. Nous complétons donc présentement l’étude NeuroPAP2 visant à évaluer la faisabilité, la tolérance et l’impact du mode NeuroPAP, un mode de ventilation permettant un ajustement continu de la PEP en fonction de l’Edi. / The optimal adjustment of ventilatory settings at the bedside is a challenge and the lack of clear targets makes setting the PEEP (positive end expiratory pressure) especially difficult. This is an important issue in pediatrics, as infants are at increased risk for alveolar derecruitment because of high chest wall compliance. To prevent this, they tend to actively maintain end expiratory lung volumes using tonic diaphragmatic activity (tonic Edi) throughout expiration. In older children, tonic Edi can be reactivated in disease states. Tonic Edi monitoring is thus a potential tool to guide PEEP titration. This thesis addresses important knowledge gaps about tonic Edi in ventilated children. We propose age-specific definitions of elevated tonic Edi in PICU patients: > 3.2 mcV in 0-1 y.o. and > 1.9 mcV in 1-18 y.o. These definitions will aid bedside identification of patient lung recruitment efforts and can prompt reassessment of optimal PEEP. We have also established that episodes of high tonic Edi are frequent in ventilated children (31% of intubated patients and 62% of patients on non-invasive ventilation). Those episodes are associated with bronchiolitis, tachypnea, and, in NIV patients, more severe hypoxemia. The majority of patients with those episodes have no contraindications to increased PEEP. These results make continuous neural adjustment of PEEP an interesting avenue. We are thus now completing this research program with a study to evaluate the feasibility, tolerance and impact of NeuroPAP, a new ventilatory mode allowing continuous neural adjustment of PEEP based on tonic Edi.

Tidigare forskning visar att ambulanssjuksköterskor upplever bristfällig utbildningsgrund samt känslor av bristande självförtroende och osäkerhet kopplat till vårdsituationer med den vuxna patienten med pågående krampanfall. Den forskning som finns etablerad omkring ambulanssjuksköterskors upplevelser av att möta den vuxna patienten med pågående kramp är dock begränsad. Ambulanssjuksköterskan har i sin yrkesutövning en förväntan på sig att inneha en handlingsberedskap för alla typer av patientärenden, så även för den vuxna patienten med pågående krampanfall. Krampanfall med tonisk-klonisk karaktär innebär ett komplext vårdmöte där ambulanssjuksköterskan måste ta ställning till multipla faktorer, både rörande en kritisk somatik samt patientens omvårdnadsmässiga behov. Studiens syfte är att beskriva ambulanssjuksköterskors upplevelse av att möta vuxna patienter med pågående epileptiskt anfall av tonisk-klonisk karaktär i prehospital miljö. Studien har genomförts som en kvalitativ, semistrukturerad intervjustudie med induktiv ansats. Genomförda intervjuer har analyserats utifrån en kvalitativ innehållsanalys och resulterade slutligen i huvudkategorin Ett vårdande som balanserar mellan trygghet och oförutsägbarhet, med efterföljande kategorier Mångbottnad upplevelse, Vårdrelationen och Prehospitalt vårdande. Resultatet visar på attambulanssjuksköterskor bär på en bred upplevelsegrund när det kommer till vårdmötet med denkrampande patienten, där känslor av osäkerhet och stress är vanlig förekommande. Ambulanssjuksköterskorna upplever även vårdmötet som utmanande i förhållande till faktorer som vårdmiljö, patientomhändertagande samt mötet med anhöriga. Ambulanssjuksköterskorna upplever att det i första hand är yrkeserfarenhet som utgör en trygghetsskapande grund i patientmötet. För att skapa förbättrade grundförutsättningar för vårdandet samt förstärka upplevelsen av trygghet för ambulanssjuksköterskor, bör ämnet lyftas tydligare inom utbildning och arbetsplatsrelaterad fortbildning. / Previous research shows that ambulance nurses experience a deficient educational basis as well as feelings of lack of self-confidence and uncertainty linked to care situations with the adult patient with ongoing seizures. However, the research that has been established about ambulance nurses' experiences of meeting the adult patient with ongoing convulsions is limited. In her professional practice, the ambulance nurse is expected to be ready to act for all types of patient matters, including for the adult patient with an ongoing seizure. Seizures with a tonic-clonic character involve a complex care encounter where the ambulance nurse must take a position on multiple factors, both concerning a critical somatic condition and the patient's nursing needs. The purpose of the study is to describe ambulance nurses' experience of meeting adult patients with ongoing epileptic seizures of tonic-clonic character in a prehospital environment. The study has been conducted as a qualitative, semi-structured interview study with an inductive approach. Conducted interviews have been analyzed based on a qualitative content analysis and finally resulted in the main category Care that balances between safety and unpredictability, with subsequent categories Multi-rooted experience, Care relationship and Pre-hospital care. The results show that ambulance nurses have a broad base of experience when it comes to the care meeting with the convulsing patient, where feelings of uncertainty and stress are common occurrences. The ambulance nurses also experience the care meeting as challenging in relation to factors such as the care environment, patient care and the meeting with relatives. The ambulance nurses feel that it is primarily professional experience that constitutes a security-creating basis in the patient encounter. In order to create improved basic conditions for care and strengthen the experience of security for ambulance nurses, the topic should be highlighted more clearly in education and workplace related continuing education.

Black choral music composers in South Africa, inspired by the few opportunities available to them until recent times, have nonetheless attempted to establish, perhaps subconsciously, some choral tradition and, in doing so, incorporate African musical elements in their works. My research traces the foundations and historical development of choral music as an art amongst Vhavenda, and the contributions made thereto by a number of past and present Venda composers that this researcher could manage to identify and trace, to the music of the people. The selected composers are Stephen Maimela Dzivhani, Matthew Ramboho Nemakhavhani, Derrick Victor Nephawe, Joseph Khorommbi Nonge, Israel Thinawanga Ramabannda and Fhatuwani Hamilton Sumbana. Through the application of multiple methodological lenses, the study sets out to analyse, describe, and interpret Venda choral music. Of particular interest is the exploration of the extent to which the ”formal” education that was brought by the Berlin Missionaries influenced Venda choral musicians, particularly the selected Venda choral music composers. Also crucial to this research is the exploration and identification of elements peculiar to indigenous Venda traditional music in the works of these composers. The question is whether it was possible for these composers to realize and utilize their potentials fully in their attempt to evoke traditional Venda music with their works, given the very limiting Western tonic sol-fa notational system they were solely working with. The project also briefly traces the place of Venda choral music within the South African music context and its role within the search for cultural identity. The research has found that the majority of Venda choral music written so far has generally not been capable of evoking indigenous Venda traditional music. Whilst these composers choose themes that are akin to their culture, social settings, legend and general communal life, the majority of the music they set to these themes does not sound African (Venda in particular) in terms of the rhythms and melodies. The majority of the compositions under scrutiny have inappropriate settings of Venda words into the melodies employed. This can be attributed to the limitations imposed by the tonic sol-fa notational system, which was the only system they were taught in the missionary schools established around Venda and which, itself, was flawed as well as the general lack of adequate music education on the part of the composers themselves. Despite these limitations and the very few opportunities available to them, Venda choral music composers nonetheless managed to lay a foundation for choral music as an art amongst their people (Vhavenda). / Art history, Visual Ars and Musicology / D. Mus

A resposta comportamental de Imobilidade Tônica (IT) ocorre em situações de perigo intenso, e em situações inescapáveis, como por exemplo,o ataque de um predador. Esta resposta caracteriza-se por perda do reflexo de endireitamento e relativa falta de responsividade aos estímulos ambientais. Estudos consistentes tem demonstrado o envolvimento de distintas áreas encefálicas na modulação desta resposta, entre elas a substância cinzenta periaquedutal, o hipotálamo e a amígdala. Considerando a amígdala em particular, estudos mostraram o envolvimento dos receptores para o fator liberador de corticotropina (CRF) dos núcleos basolateral (BLA) e central (CeA) na modulação da resposta de IT em cobaias. De fato, nas últimas décadas, várias evidências sugerem que o CRF está intimamente correlacionado com comportamento emocional associado ao medo e à ansiedade. Embora seja claro o envolvimento de receptores CRF na modulação do medo, e especificamente na modulação da IT em cobaias, ainda não está esclarecido o envolvimento dos diferentes subtipos de receptores para CRF na modulação emocional. Desta forma, o objetivo deste trabalho foi investigar o envolvimento dos receptores específicos para o fator liberador de corticotropina, CRF1 e CRF2 dos núcleos basolateral (BLA) e central da amígdala (CeA) na modulação da resposta de IT em cobaias.Para atingir estes objetivos, grupos independentes de cobaias, com implante de cânulas-guias dirigidas para o BLA ou para o CeA foram avaliadas no teste de imobilidade tônica, antes e depois da administração dos antagonistas específicos para receptores CRF1 (CP-376395) ou para receptores CRF2 (Astressin 2B), ou depois da administração de CRF precedido ou não dos antagonistas CRF1 ou CRF2. Em adição, para avaliar se as drogas utilizadas alteraram a atividade locomotora, foi realizado o teste do campo aberto, por 5 minutos, após a administração dos antagonistas para receptores CRF1 (CP-376395) e CRF2 (Astressin 2B), em doses capazes de alterar a resposta de IT em cobaias, e de CRF precedido por antagonista CRF1 ou CRF2. Os resultados deste trabalho mostram que o bloqueio dos receptores CRF1 e CRF2 no BLA e no CeA reduziram a duração da resposta defensiva de imobilidade tônica (IT) em cobaias. Inversamente, a ativação destes receptores no BLA e no CeA aumentou o tempo de IT, demonstrado pela administração de CRF nestas regiões amigdalóides. Ainda, os antagonistas específicos para receptores CRF1 e CRF2 foram capazes de bloquear o aumento da duração da IT induzida pelo CRF administrado no mesmo sítio. Estes resultados sugerem que o efeito promovido pelo CRF no BLA e no CeA ocorre por atuação conjunta em receptores CRF1 e CRF2. Em adição, é importante ressaltar que as drogas, nas doses utilizadas neste estudo, não promoveram alteração da resposta motora, desde que não alteraram a atividade no teste do campo aberto, o que por si só, poderia alterar a resposta de IT. Assim, é possível que sugerir que o bloqueio específico de receptores CRF1 e CRF2 do BLA e do CeA promovem redução do medo e/ou da ansiedade, resultando em redução da resposta de IT em cobaias. / The tonic immobility response (TI ) occurs in inescapable situations of intense danger, such as the predator attack. This response is characterized by loss of righting reflex and the relative lack of responsiveness to environmental stimuli. Consistent studies have demonstrated the involvement of different brain areas to modulate this defensive behavior, including the periaqueductal gray matter, hypothalamus and amygdala. Whereas the amygdala in particular, studies have shown the involvement of receptors for corticotropin-releasing factor (CRF) of the central (CeA) and basolateral (BLA) nuclei os amygdala in TI modulating in guinea pigs. Indeed, in recent decades, several evidences suggest that CRF is closely correlated with emotional behavior associated with fear and anxiety. While it is clear the involvement of CRF receptors in the modulation of fear, and specifically in the modulation of TI, it is still unclear the involvement of different subtypes of CRF receptors in the emotional modulation. Thus, the aim of this study was to investigate the involvement of specific receptors for corticotropin-releasing factor, CRF1 and CRF2of BLA and of CeA in modulating the TI response in guinea pigs. To achieve these objectives, independent groups of guinea pigs were implanted with guide cannulae aimed for BLA or CeA were evaluated in the test of tonic immobility before and after the administration of specific antagonists of CRF1 receptors (CP- 376395) or CRF2 receptors (Astressin 2B), or after the administration of CRF preceded by CRF1or CRF2 antagonists, or CRF per se. In addition, to assess whether the drugs used altered locomotor activity, the open field test, for 5 minutes was performed after administration of antagonists for CRF1 receptors (CP- 376395) and CRF2 (Astressin 2B), at doses that alter the TI response in guinea pigs, and the CRF agonist preceded by CRF1 or CRF2. These results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA reduced the duration of the defensive response of tonic immobility (TI) in guinea pigs. In contrast, activation of these receptors in the BLA and CeA increased the TI duration, demonstrated by administration of CRF in these amygdaloid regions. Also, specific antagonists for CRF1 and CRF2 receptors were able to block the increase in the TI response induced by CRF administered in the same structure. These results suggest that the effect promoted by CRF in the BLA and CeA is by joint performance of CRF1 and CRF2 receptors. Additionally, it is important to note that the drugs, in the doses used in this study, did not promote change in the motor response, since it did not alter the activity in the open field test, which by itself could alter the TI response. Thus, it is possible to suggest that the specific blockade of CRF1 and CRF2 receptors in the BLA and CeA promote reduction of fear and/or anxiety, resulting in reduced TI response in guinea pigs.

A resposta comportamental de Imobilidade Tônica (IT) ocorre em situações de perigo intenso, e em situações inescapáveis, como por exemplo,o ataque de um predador. Esta resposta caracteriza-se por perda do reflexo de endireitamento e relativa falta de responsividade aos estímulos ambientais. Estudos consistentes tem demonstrado o envolvimento de distintas áreas encefálicas na modulação desta resposta, entre elas a substância cinzenta periaquedutal, o hipotálamo e a amígdala. Considerando a amígdala em particular, estudos mostraram o envolvimento dos receptores para o fator liberador de corticotropina (CRF) dos núcleos basolateral (BLA) e central (CeA) na modulação da resposta de IT em cobaias. De fato, nas últimas décadas, várias evidências sugerem que o CRF está intimamente correlacionado com comportamento emocional associado ao medo e à ansiedade. Embora seja claro o envolvimento de receptores CRF na modulação do medo, e especificamente na modulação da IT em cobaias, ainda não está esclarecido o envolvimento dos diferentes subtipos de receptores para CRF na modulação emocional. Desta forma, o objetivo deste trabalho foi investigar o envolvimento dos receptores específicos para o fator liberador de corticotropina, CRF1 e CRF2 dos núcleos basolateral (BLA) e central da amígdala (CeA) na modulação da resposta de IT em cobaias.Para atingir estes objetivos, grupos independentes de cobaias, com implante de cânulas-guias dirigidas para o BLA ou para o CeA foram avaliadas no teste de imobilidade tônica, antes e depois da administração dos antagonistas específicos para receptores CRF1 (CP-376395) ou para receptores CRF2 (Astressin 2B), ou depois da administração de CRF precedido ou não dos antagonistas CRF1 ou CRF2. Em adição, para avaliar se as drogas utilizadas alteraram a atividade locomotora, foi realizado o teste do campo aberto, por 5 minutos, após a administração dos antagonistas para receptores CRF1 (CP-376395) e CRF2 (Astressin 2B), em doses capazes de alterar a resposta de IT em cobaias, e de CRF precedido por antagonista CRF1 ou CRF2. Os resultados deste trabalho mostram que o bloqueio dos receptores CRF1 e CRF2 no BLA e no CeA reduziram a duração da resposta defensiva de imobilidade tônica (IT) em cobaias. Inversamente, a ativação destes receptores no BLA e no CeA aumentou o tempo de IT, demonstrado pela administração de CRF nestas regiões amigdalóides. Ainda, os antagonistas específicos para receptores CRF1 e CRF2 foram capazes de bloquear o aumento da duração da IT induzida pelo CRF administrado no mesmo sítio. Estes resultados sugerem que o efeito promovido pelo CRF no BLA e no CeA ocorre por atuação conjunta em receptores CRF1 e CRF2. Em adição, é importante ressaltar que as drogas, nas doses utilizadas neste estudo, não promoveram alteração da resposta motora, desde que não alteraram a atividade no teste do campo aberto, o que por si só, poderia alterar a resposta de IT. Assim, é possível que sugerir que o bloqueio específico de receptores CRF1 e CRF2 do BLA e do CeA promovem redução do medo e/ou da ansiedade, resultando em redução da resposta de IT em cobaias. / The tonic immobility response (TI ) occurs in inescapable situations of intense danger, such as the predator attack. This response is characterized by loss of righting reflex and the relative lack of responsiveness to environmental stimuli. Consistent studies have demonstrated the involvement of different brain areas to modulate this defensive behavior, including the periaqueductal gray matter, hypothalamus and amygdala. Whereas the amygdala in particular, studies have shown the involvement of receptors for corticotropin-releasing factor (CRF) of the central (CeA) and basolateral (BLA) nuclei os amygdala in TI modulating in guinea pigs. Indeed, in recent decades, several evidences suggest that CRF is closely correlated with emotional behavior associated with fear and anxiety. While it is clear the involvement of CRF receptors in the modulation of fear, and specifically in the modulation of TI, it is still unclear the involvement of different subtypes of CRF receptors in the emotional modulation. Thus, the aim of this study was to investigate the involvement of specific receptors for corticotropin-releasing factor, CRF1 and CRF2of BLA and of CeA in modulating the TI response in guinea pigs. To achieve these objectives, independent groups of guinea pigs were implanted with guide cannulae aimed for BLA or CeA were evaluated in the test of tonic immobility before and after the administration of specific antagonists of CRF1 receptors (CP- 376395) or CRF2 receptors (Astressin 2B), or after the administration of CRF preceded by CRF1or CRF2 antagonists, or CRF per se. In addition, to assess whether the drugs used altered locomotor activity, the open field test, for 5 minutes was performed after administration of antagonists for CRF1 receptors (CP- 376395) and CRF2 (Astressin 2B), at doses that alter the TI response in guinea pigs, and the CRF agonist preceded by CRF1 or CRF2. These results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA reduced the duration of the defensive response of tonic immobility (TI) in guinea pigs. In contrast, activation of these receptors in the BLA and CeA increased the TI duration, demonstrated by administration of CRF in these amygdaloid regions. Also, specific antagonists for CRF1 and CRF2 receptors were able to block the increase in the TI response induced by CRF administered in the same structure. These results suggest that the effect promoted by CRF in the BLA and CeA is by joint performance of CRF1 and CRF2 receptors. Additionally, it is important to note that the drugs, in the doses used in this study, did not promote change in the motor response, since it did not alter the activity in the open field test, which by itself could alter the TI response. Thus, it is possible to suggest that the specific blockade of CRF1 and CRF2 receptors in the BLA and CeA promote reduction of fear and/or anxiety, resulting in reduced TI response in guinea pigs.

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2018-08-06T13:39:12Z No. of bitstreams: 1 GABRIELA TORNQUIST MAZZAFERRO.pdf: 6634163 bytes, checksum: b3be1b37f9ceeae1f0fcfe8335b5bc71 (MD5) / Made available in DSpace on 2018-08-06T13:39:12Z (GMT). No. of bitstreams: 1 GABRIELA TORNQUIST MAZZAFERRO.pdf: 6634163 bytes, checksum: b3be1b37f9ceeae1f0fcfe8335b5bc71 (MD5) Previous issue date: 2017-12-18 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES# / #2075167498588264571# / #600 / This study aims to describe, analyze and formalize the behavior of the non-final and final post-tonic mid-vowels from the Portuguese spoken language in the extreme south part of Brazil, more specifically, the five bordering cities in Uruguay: Acegua, Chui, Jaguarao, Quarai and Santana do Livramento. This interest has come as a necessity for the mapping of the Portuguese spoken language in communities which are on the border of Uruguay, a Spanish speaking country, and taking into consideration that the vowel systems of the Brazilian Portuguese language (BP) and the Spanish language show different structures and functioning: seven of them are the phonological vowels of BP language and, according to Câmara Jr. (1977), in the non-final post-tonic position there is an operation of four vowels: /a/, /i/, /u/, /e/, which passes to only three in the final atonic position: /a/, /i/, /u/, due to the neutralization process. Differently, the Spanish language, in all of its phonological positions, presents the system of five vowels: /a/, /i/, /u/, /e/, /o/, regardless of the tonicity of the syllable. It was assumed as a research hypothesis, which considered the studies such as Vieira (1994, 2002, 2009) and Machry da Silva (2009), that the speakers of the Brazilian cities bordering Uruguay have presented differences in the use of the non-final and final atonic vowels when compared to the Portuguese spoken language from the remaining part of Rio Grande do Sul and Brazil due to the influence of Spanish phonology. Combined with limited studies focused on the research of the spoken BP in the southern border of the country, this research is based on Variationist Sociolinguistics with its particularity of proposing phonological analysis and the formalization of the results based on the Stochastic Optimality Theory. The corpus of the study consisted of data from 40 (forty) informants - eight informants from each of the cities previously mentioned. Two types of procedures were proposed for data collection: a specific instrument to obtain non-final post-tonic vowels and a sociolinguistic interview to obtain final post-tonic vowels. The data was transcribed, signed and submitted to the RBRUL computer software with the control of linguistic and extralinguistic variables. Statistical results indicated that these variables were relevant for the elevation of the non-final post-tonic vowels process in the five cities surveyed. Yet, they seem to indicate that the motivation for the occurrence (or not) of the process is found when in contact with the Spanish language, a homogenized factor, which is present in all of the border cities. The elevation process of the post-tonic vowels was present in all of the border cities: regarding the non-final post-tonic vowels, the indices were lower than the remaining of the state and the country, being more effective with the mid-vowel /o/ than the mid-vowel /e/, which corroborates the proposal of Camara Jr. (1977). Regarding the final post-tonic vowels, the effectiveness of the process reached levels above 70% for the vowel /e/ and 95% for the vowel /o/ with categorical results for the cities of Chui and Jaguarao, which provided evidence that this process may be indicating a change in the BP language on the border. The formalizations supported by the Stochastic Optimality Theory showed that by means of restrictions and hierarchization is possible to represent the atonicity as a motivator of the study process as well as to express the tendency for vowel elevation in BP language as a result of the neutralization process. The analysis of the data suggests that the behavior of the post-tonic vowels on the border communities with cities of Uruguay presents some particular features that keep the spoken Portuguese language on the border distant from the spoken BP of the remaining part of the state and the country. / Este estudo descreve, analisa e formaliza o comportamento das vogais médias postônicas não finais e finais no português falado no extremo sul do Brasil, mais especificamente em cinco cidades que fazem fronteira com o Uruguai: Aceguá, Chuí, Jaguarão, Quaraí e Santana do Livramento. O interesse está na necessidade de um mapeamento do português falado em comunidades que fazem fronteira com o Uruguai, país de fala espanhola, já que os sistemas vocálicos do português brasileiro (PB) e do espanhol mostram diferentes estruturas e funcionamento: sete são as vogais fonológicas do PB e, segundo Câmara Jr. (1977), na posição postônica não final há o funcionamento de quatro vogais: /a/, /i/, /u/, /e/, passando para apenas três na posição átona final: /a/, /i/, /u/, em virtude de um processo de neutralização; diferentemente, o espanhol apresenta, em todas as posições fonológicas, o sistema de cinco vogais: /a/, /i/, /u/, /e/, /o/, independentemente da tonicidade da sílaba. Assumiu-se como hipótese de pesquisa, considerando estudos como o de Vieira (1994, 2002, 2009) e de Machry da Silva (2009), que os falantes das cidades brasileiras fronteiriças com o Uruguai, por influência da fonologia do espanhol, apresentam diferenças no emprego das vogais átonas não finais e finais, em se comparando com o português falado no restante do Rio Grande do Sul e do Brasil. Aliando-se aos estudos voltados para a investigação do PB falado na Fronteira Sul do País, esta investigação está fundamentada na Sociolinguística Variacionista, com a particularidade de propor a análise fonológica e a formalização dos resultados com base na Teoria da Otimidade Estocástica. O corpus do estudo foi constituído por dados de 40 (quarenta) informantes – oito informantes de cada uma das cidades. Foram propostos dois tipos de procedimentos para a coleta dos dados: um instrumento específico para a obtenção de vogais postônicas não finais e uma entrevista sociolinguística para a obtenção de vogais postônicas finais. Os dados foram transcritos, fichados e submetidos ao programa computacional RBRUL, com o controle de variáveis linguísticas e extralinguísticas. Os resultados estatísticos indicaram que essas variáveis se mostraram relevantes para o processo de elevação das vogais médias postônicas não finais nas cinco cidades pesquisadas, mas parecem indicar que a motivação para a ocorrência (ou não) do processo se encontra no contato com o espanhol, fator homogeneizado, tendo em vista o fato de estar presente em todas as cidades fronteiriças. O processo de elevação das vogais postônicas mostrou-se presente em todas as cidades de fronteira: quanto às vogais postônicas não finais, os índices foram inferiores ao restante do Estado e País, sendo mais efetivo com a vogal média /o/ do que com a média /e/, o que corrobora a proposta de Câmara Jr. (1977); quanto às vogais postônicas finais, a efetivação do processo alcançou índices acima de 70% para a vogal /e/ e de 95% para a vogal /o/, com resultados categóricos para as cidades de Chuí e Jaguarão, trazendo evidências de que esse processo de variação pode estar indicando uma mudança no PB da fronteira. As formalizações com o suporte da Teoria da Otimidade Estocástica evidenciaram que, por meio de restrições e de sua hierarquização, é possível representar a atonicidade como motivadora do processo alvo do estudo, bem como expressar a tendência à elevação vocálica no PB como resultante do processo de neutralização. As análises dos dados permitem afirmar que o comportamento das vogais médias postônicas nas comunidades de fronteira com cidades do Uruguai apresenta especificidades que distanciam o português fronteiriço do PB falado no restante do Estado e do País.