After injury, dorsal root (DR) axons regenerate in the peripheral nervous system (PNS), but turn around or stop at the dorsal root entry zone (DREZ), the entrance into the central nervous system (CNS). Examination of the dynamic axon regeneration that occurs following injury to the DR provides the opportunity to advance our understanding of what happens to sensory axons as they approach and arrive at the DREZ and expands our knowledge of sensory axon regeneration failure at the entrance to the spinal cord. Additionally, findings from these studies may offer potential avenues to provide insight into regeneration failure elsewhere in the central nervous system. Nevertheless, our understanding of the cellular and molecular processes underlying the failure of DR axons to regenerate through the DREZ is incomplete. The goal of my thesis work was to determine whether application of the time lapse-in vivo imaging technique is feasible and useful in studying dorsal root regeneration. I have also applied recently developed post-mortem analyses to the axons monitored in vivo, which provided additional insights into the mechanisms that prevent axon regeneration at the DREZ. Results in Chapters 2 and 3 demonstrate that wide-field microscopy is indeed feasible and useful for monitoring regenerating sensory axons immediately before, during, and in the days to weeks after lumbar (L5) DR crush. I was surprised to find that most axons were immobilized abruptly and chronically at the CNS portion of the DREZ, with their axon tips and shafts exhibiting features of differentiated nerve terminals. This observation raises the possibility, which has not been appreciated previously, that DR axons stop at the DREZ because their regeneration is terminated prematurely by forming synaptic contacts with unidentified postsynaptic cells. To confirm the immobilization of DR axons at the DREZ, I applied two-photon microscopy to examine the axon behavior at the DREZ at high resolution. Results described in Chapter 4 confirm those obtained with the time-lapse imaging performed with wide-field microscopy: axons arrested soon after their arrival at the DREZ did not exhibit even subtle movements. Light microscopic analyses of the failed axon tips monitored in vivo demonstrated that almost all axons stopped at the CNS territory of the DREZ, and that axon tips and adjacent shafts intensely immunolabeled with synapse markers. Ultrastructural analyses revealed that numerous axonal profiles had the characteristic features of pre- but not postsynaptic endings. Findings from these studies lead us to speculate that most, if not all, dorsal root axons become arrested as they enter the CNS territory of the DREZ by forming presynaptic terminals on non-neuronal cellular elements that differ from the dystrophic-like endings formed by a few axons. In the chapter 5, I discuss what I have found to be the key factors for successful monitoring of regenerating dorsal root axons in living animals; the feasibility, usefulness and limitations of the available techniques and future directions for studying spinal root injury and regeneration. My thesis work represents the first to employ in vivo imaging to study DR regeneration directly in living animals. This approach was more challenging to develop than we had anticipated but provided unexpected insights into the mechanisms preventing sensory nerve regeneration. Continuous application of the powerful in vivo imaging technique in combination with conventional analyses will elucidate critically important issues that previous static analyses could not decipher. / Cell Biology

Shark tagging is used as a source of data for shark migration and behaviors. Different tags can collect temperature, salinity, or depth data points while the shark is in motion. There are a variety of shark tagging methods used to monitor sharks. Of these methods, shark bolting has caused some concern. Shark bolting is the method of drilling holes into the first dorsal fin of pelagic sharks and placing steel screws into the fin to secure a satellite (SAT) tag. Bolted SAT tags cause concern due to the limited ways of removal, high probability of excessive biofouling, infections, and increased drag while swimming in many species of sharks. The objective of this study is to assess if bolting is a non-impact shark tagging method in terms of resulting shark health and behavior and, further, whether it should be considered a humane or inhumane practice by examining the present knowledge of dorsal fin anatomy and functionality.

Thèse réalisée en cotutelle avec l'Université catholique de Louvain. / Ce travail de thèse s’est intéressé à la plasticité cérébrale associée à la privation/restauration visuelle. A travers deux études transversales utilisant l’imagerie par résonance magnétique fonctionnelle auprès d’un groupe de participants présentant une cécité congénitale ou précoce (ainsi qu’auprès d’un groupe contrôle de participants voyants), nous avons tenté de caractériser la manière dont le cortex occipital - typiquement dédié au traitement de l’information visuelle - se réorganise afin de traiter différents stimuli auditifs. Nous démontrons qu’en cas de cécité précoce, différentes régions du cortex occipital présentent une préférence fonctionnelle pour certains types de stimuli non-visuels, avec une spécialisation fonctionnelle qui respecte celle de régions typiquement impliquées dans le traitement d’informations similaires en vision. Ces découvertes constituent une avancée conceptuelle concernant le rôle joué par les contraintes intrinsèques d’une part, et par l’expérience d’autre part, dans l’émergence de réponses sensorielles et fonctionnelles du cortex occipital. D’une part, l’observation de réponses occipitales à la stimulation auditive chez le non-voyant précoce (réorganisation transmodale) rend compte de la capacité du cortex occipital à réorienter sa modalité sensorielle préférentielle en fonction de l’expérience. D’autre part, l’existence de modules cognitifs spécialisés dans le cortex occipital du non-voyant précoce, semblables à ceux du cerveau voyant, démontre les contraintes intrinsèques imposées à une telle plasticité. Dans une étude de cas longitudinale, nous avons également exploré comment les changements plastiques associés à la cécité interagissent avec une récupération visuelle partielle à l’âge adulte. Nous avons réalisé des mesures pré et post-opératoires auprès d’un patient ayant récupéré la vision, en combinant les techniques comportementales ainsi que de neuroimagerie fonctionnelle et structurelle afin d’investiguer conjointement l’évolution de la réorganisation transmodale et de la récupération des fonctions visuelles à travers le temps. Nous démontrons que les changements structurels et fonctionnels caractérisant le cortex occipital du non-voyant sont partiellement réversibles suite à une récupération visuelle à l’âge adulte. De manière générale, ces recherches témoignent de l’importante adaptabilité du cortex occipital aux prises avec des changements drastiques dans l’expérience visuelle. / The present Ph.D. work was dedicated to the study of experience-dependent brain plasticity associated with visual deprivation/restoration. In two cross-sectional studies involving the use of functional magnetic resonance imaging in a group of participants with congenital or early blindness (and in a control group of sighted participants), we attempted to characterize the way the occipital cortex - typically devoted to vision – reorganizes itself in order to process different auditory stimuli. We demonstrate that in case of early visual deprivation, distinct regions of the occipital cortex display a functional preference for specific non-visual attributes, maintaining a functional specialization similar to the one that characterizes the sighted brain. Such studies have shed new light on the role played by intrinsic constraints on the one side, and experience on the other, in shaping the modality- and functional tuning of the occipital cortex. On the one hand, the observation of occipital responses to auditory stimulation (crossmodal plasticity) highlights the ability of the occipital cortex to reorient its preferential tuning towards the preserved sensory modalities as a function of experience. On the other hand, the observation of specialized cognitive modules in the occipital cortex, similar to those observed in the sighted, highlights the intrinsic constraints imposed to such plasticity. In a longitudinal single-case study, we further explored how the neuroplastic changes associated with blindness may interact with the newly reacquired visual inputs following partial visual restoration in adulthood. We performed both pre- and post-surgery measurements in a sight-recovery patient combining behavioral, neurostructural and neurofunctional methods in order to jointly investigate the evolution of crossmodal reorganization and visual recovery across time. We demonstrate that functional and structural changes evidenced in the visually-deprived occipital cortex can only partially reverse following sight restoration in adulthood. Altogether, our findings demonstrate the striking adaptability of the occipital cortex facing drastic changes in visual experience.

Les comportements orientés vers un but sont complexes et font appel à un grand nombre de processus cérébraux. Le cortex préfrontal médian (mPFC) apparaît comme une structure clef dans la réalisation de ces comportements de par son rôle dans la planification. De plus, il existe au sein du mPFC des cellules signalant les lieux à forte valeur motivationnelle. L’activité de ces neurones pourrait être essentielle à la mise en place d’un comportement spatial dirigé vers un but. S’orienter vers un but nécessite aussi la construction d’une représentation stable de l’environnement, qui repose sur l’activité de l’hippocampe (HPC). Néanmoins, peu de travaux ont analysé le rôle respectif de ces deux structures, et leurs interactions, lors de l’acquisition et de la consolidation d’une stratégie comportementale orientée vers un but. L’objectif des recherches réalisées au cours de ma thèse est donc d’étudier l’implication de l’hippocampe et du cortex préfrontal médian du rat dans ce processus. Notre première étude a montré l’existence d’un codage prospectif au sein des neurones du mPFC durant la réalisation d’une tâche de mémoire de travail.L’activité des neurones signale à la fois, la séquence temporelle comportementale, et l’anticipation de la récompense, et jouerait ainsi un rôle dans les fonctions exécutives. Dans la deuxième étude, nous nous sommes intéressés aux structures cérébrales impliquées dans la mise à jour de la valence du but ainsi que dans sa rétention à long terme. Nos résultats ont montré que l’inactivation de l’hippocampe intermédiaire provoque des déficits dans le traitement à court terme d’un changement de valence. En revanche, l’inactivation du mPFC empêche le stockage à long terme de ce changement. L’activité de ces deux structures serait donc essentielle pour effectuer une mise à jour en temps réel de la valence d’un but et pour sa consolidation en mémoire à long terme. Leur interaction permettrait d’adapter rapidement et de façon durable la stratégie comportementale de l’animal face aux changements de l’environnement. / Goal-directed behaviors are complex and involve a variety of cognitive processes. Medial prefrontal cortex (mPFC) plays a key role in behavioral planning. More over, cells in the rat mPFC show specific firing modulations at location with a high motivational value. Such neuronal activity could be essential for the setting up installation of a goal-directed behavior. Further more, navigating to a spatial goal requires the building of a stable presentation of the environment which is hippocampus-dependent. So far however, only few studies have addressed the respective role of these two structures, and their interaction, during the acquisition and the consolidation of a goal directed-behavior. The work conducted during my PhD thesis aimed at studying the role of hippocampus and prefrontal cortex in this process. In a first study,we showed the existence of a prospective coding by mPFC neurons when the rat performs a working memory task. Neuronal activity signals both, the temporal sequence of the behavior, and the prediction of reward. These neurons would play a role inexecutive functions. In a second study, we focused on cerebral structures involved in the updating of the value of a goal as well as in its long-term retention. Our results showed that the inactivation of the intermediate hippocampus causes deficit in the short-term processing of a change in the goal value. On the other hand, the inactivation of the mPFC prevents long-term consolidation of this change. Integrity of this two structures would therefore be essential to perform an on-line updating of the goal value and for its long-term consolidation. Their interaction would be necessary to rapidly adapt, and in a lasting manner, the behavioral strategy of the animal when it faces an environmental change.

Há estudos que mostraram que o ácido N-metil-D-aspártico (NMDA), microinjetado nas estruturas do teto mesencefálico (corpos quadrigêmeos) de ratos evoca comportamentos defensivos do tipo pânico que podem ser seguidos por uma resposta antinociceptiva. Tem sido sugerido que respostas defensivas relacionadas ao medo organizadas por neurônios do tronco cerebral podem ser moduladas por projeções ascendentes mediadas pelo neurotransmissor 5-hidroxitriptamina (5-HT) do núcleo dorsal da rafe (NDR), e fenômenos antinociceptivos induzidos pelo medo inato podem ser organizados por vias serotoninérgicas descendentes também originadas no NDR. Os neurônios do NDR que originam tais conexões, por sua vez, podem ser moduladas por monoaminas que recrutam receptores 5-HT2A localizados no NDR. Não obstante, háuma escassez de estudos mostrando o papel dos receptores 5-HT2A do NDR na modulação do comportamento do tipo pânico e da antinocicepção induzida pelo medo inato organizados nos colículos superiores e inferiores. O objetivo deste estudo foi investigar a participação dos receptores 5-HT2A do NDR na modulação do comportamento de defesa organizado pelos corpos quadrigêmeos e da antinocicepção induzida pelo medo evocados por microinjeções de NMDA nos corpos quadrigêmeos. No experimento I, os animais receberam microinjeção de veículo (NaCl 0,9% / 0,2?L) ou 6, 9 e 12 nmol NMDA no CI. No experimento II, foi realizado o pré-tratamento do NDR com microinjeções de veículo ou o antagonista seletivo do receptor 5HT2A (R-96544) nas concentrações de 5, 10 e 15 nM. Dez minutos depois, o NMDA na dose mais efetiva (12 nmol) foi injetado no CI. Em ambos os experimentos, as respostas defensivas foram analisadas quantitativamente durante 10 min e, em seguida, as latências de retirada de cauda foram medidas a intervalos de 10 min durante 70 min. No experimento III, os animais receberam microinjeção de salina fisiológica ou NMDA (6, 9 e 12 nmol) nas cpSC. No experimento IV, a dose mais efetiva de NMDA (12 nmol) ou veículo foi precedida por microinjeções de veículo ou antagonista seletivo do receptor 5HT2A (R- 96544) em diferentes concentrações, 0.5, 5 e 10 nM. Ambos os efeitos pró-eversivos e antinociceptivos provocados pelas injecções intra-cpCS de NMDA foram atenuados pelo pré-tratamento do NDR com R-96544. No experimento V, a análise morfológica mostrou que os receptores 5-HT2A estão presentes nos interneurônios GABAérgicos do NDR. Em conjunto, esses achados sugerem que o bloqueio dos receptores 5-HT2A no NDR é capaz de atenuar tanto o comportamento defensivo do tipo pânico quanto a antinocicepção induzida pelo medo organizada pelos corpos quadrigêmeos. / There are studies that suggest that N-methyl-D-aspartic acid (NMDA) microinjected into the midbrain tectum structures, such corpora quadrigemina, of rats evokes panic-like defensive behaviours that can be followed by an antinociceptive response. It has been suggested that fear-related defensive responses organised by brainstem neurons can be modulated by ascending projections mediated by the neurotransmitter 5-hydroxytryptamine (5-HT) of the dorsal raphe nucleus (DRN), and phenomena of innate fear-induced antinociception can be organised by descending serotonergic pathways also originating from the DRN. The DRN neurons that give rise to such connections, in turn, can be moduled by monoamines that recruit 5-HT2A receptors located in the DRN. Nevertheless, there is a shortage of studies showing the role of DRN 5-HT2A receptors in the modulation of panic-like behaviour and innate fearinduced antinociception organised by superior and inferior colliculi. The purpose of this study was to investigate the participation of DRN 5-HT2A receptors in the modulation of panic-like behaviour and antinociception evoked by corpora quadrigemina injections of NMDA. In experiment I, the animals received microinjection of vehicle (0.9%NaCl/0.2?L) or 6, 9 and 12 nmol NMDA into the IC. In experiment II, it was performed the pretreatment of DRN with microinjections of vehicle or the 5HT2A receptor selective antagonist (R-96544) in a concentration of 5, 10 and 15 nM. Ten minutes later, NMDA at the most effective dose (12nmol) was injected in the IC. In both experiments, the defensive responses were quantitatively analysed for 10 min and then the tail-flick withdrawal latencies were measured at 10 min-intervals for 70 min. In experiment III, the animals received microinjection of physiological saline or NMDA (6, 9 and 12 nmol) into the deep layers of SC (dlSC). In experiment IV, the most effective dose of NMDA (12 nmol) or vehicle was preceded by microinjections of vehicle or 5HT2A receptor selective antagonist (R-96544) at different concentrations (0.5, 5, and 10 nM). Both proaversive and antinociceptive effects elicited by intra-dlSC injections of NMDA were attenuated by the pretreatment of the DRN with R-96544. In experiment V, the morphological analysis showed that 5-HT2A receptors are present in GABAergic interneurons in the DRN. Taken together, these findings suggest that the blockade of DRN 5-HT2A receptors decreased both panic attack-like defensive behaviour and fear- induced antinociception organised by the corpora quadrigemina neurons.

La peur est ce qui permet de réagir à un stimulus aversif par une réponse de défense adaptée à la situation. Elle peut être générée par un ensemble de stimuli naturellement aversifs ou par des stimuli ayant acquis une valeur aversive par apprentissage associatif. Cette thèse a pour but d'étudier les caractéristiques et modifications de la réponse de peur à ces deux types de stimuli au cours de l'ontogenèse. Les études présentées ici utilisent un conditionnement de peur à l'odeur chez le rat qui associe une odeur à un stimulus aversif et permet d'induire très rapidement et durablement des mémoires de peur à l'odeur. La réponse de défense peut alors être étudiée à la fois envers l'odeur apprise et envers le stimulus naturellement aversif. Nous montrons en particulier que la réponse de peur à l'odeur apprise présente un décours temporel corrélé à la durée de l'intervalle de temps entre l'odeur et le stimulus aversif, permettant d'affirmer que les animaux mémorisent et estiment le temps, et ce dès les premiers âges étudiés, avant la maturation des structures cérébrales classiquement impliquées dans cette mémoire temporelle. Par ailleurs, nous nous sommes intéressés aux vocalisations ultrasonores émises en réponse au stimulus aversif et à leur modification au cours de l'ontogenèse. Nous avons mis en évidence deux types de vocalisations chez le raton, dont les caractéristiques et critères d'induction laissent présager un rôle différentiel qui reste à explorer. L'ensemble de ces travaux soulignent que, même si les réponses de défense du rat changent au cours du développement, la capacité à produire ces réponses de manière temporellement adaptée est observée dès le plus jeune âge / Fear allows individuals to react to an aversive stimulus by a defense response adapted to the situation. It can be triggered by naturally aversive stimuli or in response to stimuli that acquired an aversive valence through associative learning. This thesis investigated the characteristics and modifications of fear responses to these two types of stimuli throughout ontogeny. The studies presented here used olfactory fear conditioning in rat, in which an odor is paired with an aversive event and allows to rapidly induce long lasting odor fear memories. Defense responses can then be studied both to the learned odor and to the naturally aversive stimulus. We showed in particular that fear response to the learned odor presents a temporal pattern correlated with the duration of the time interval between the odor and the aversive event, showing that rats can learn about time and they do so at the youngest ages studied here, before the maturation of the brain structures classically involved in interval timing. We also studied the ultrasonic vocalizations emitted in response to the aversive stimulus and their changes throughout ontogeny. We described two types of vocalizations in pups that differ in their characteristics and emission context, suggesting they could have different functions, which needs further exploration. These thesis findings highlight that although the rat’s defense responses changes through ontogeny, the ability to produce temporally adapted responses occurs from the youngest age

A substância cinzenta periaquedutal dorsal (SCPd) é considerada uma das principais estruturas do teto mesencefálico envolvida no substrato neural da aversão a estímulos proximais. GABA e 5-HT são apontados como neurotransmissores envolvidos na modulação das respostas defensivas elaboradas na SCPd. Recentemente, mecanismos neurocininérgicos também têm sido propostos como mediadores das reações de defesa organizadas nessa estrutura. O objetivo do presente estudo foi avaliar o envolvimento dos receptores NK-1 e NK-3 da SCPd no comportamento defensivo induzido pela estimulação elétrica dessa região em ratos com e sem experiência prévia ao condicionamento contextual aversivo. Para isso, os limiares aversivos de congelamento e fuga foram medidos durante a estimulação elétrica da SCPd em ratos ingênuos e em animais submetidos previamente ao procedimento de condicionamento contextual aversivo. A mediação destas repostas defensivas pelos receptores NK-1 e NK-3 foi avaliada pela injeção local de spantide (100 pmol/0,2 L) e SB 222200 (50 e 100 pmol/0,2 L), antagonistas seletivos de receptores NK-1 e NK-3, respectivamente. Os resultados mostraram que a injeção intra-SCPd de spantide aumentou os limiares aversivos determinados pela estimulação elétrica da SCPd em animais ingênuos e com experiência aversiva prévia. Injeções similares de 100 pmol de SB 222200 na SCPd também causaram um aumento nos limiares de congelamento e fuga. Entretanto, esses efeitos devem ser atribuídos a um déficit motor causado por essa dose da droga, uma vez que SB 222200 na dose de 100 pmol, reduziu significativamente a atividade motora dos animais submetidos ao teste do campo aberto. Estes resultados sugerem que receptores NK-1, mas não NK-3, estão envolvidos na mediação do comportamento defensivo induzido pela estimulação elétrica da SCPd. / The dorsal periaqueductal gray (dPAG) constitutes the main structure of the neural substrate for the defensive response to proximal aversive stimuli. It is well established that GABA and 5-HT are important neuromediators of the defense reaction at the dPAG level but neurokinin-mediated mechanisms have also been recently implicated in these processes. The aim of the present investigation was to examine the involvement of NK-1 and NK-3 receptors of the dPAG in the unconditioned defensive behaviors induced by electrical stimulation of the dPAG of rats with and without previous experience with contextual fear conditioning. For this, aversive thresholds were measured as the lowest intensity of electric current to produce freezing and escape behaviors using a procedure of gradual increases of the electrical stimulation of the dPAG. These thresholds were also measured in rats previously submitted to a contextual fear conditioning procedure. The mediation of these defensive responses by NK-1 and NK-3 receptors of the dPAG was evaluated by local injections of spantide (100 pmol/0.2 L) and SB 222200 (50 and 100 pmol/0.2 L), selective antagonists of NK-1 and NK-3 receptors, respectively. The present results showed that spantide injections into the dPAG increased the aversive thresholds (anti-aversive effects) determined by stimulation of the dPAG in naive and in animals subjected previously to the contextual fear conditioning. Similar injections of SB 222200 100 pmol into the dPAG increased the freezing and escape thresholds. However, this effect can be attributable to a motor deficit since this dose of SB 222200 decreased the exploratory activity of the animals subjected to the open field test. These results suggest that NK-1 receptors, but not NK-3 receptors, are involved in the mediation of the defensive behaviors induced by electrical stimulation of the dPAG.

O comportamento emocional tem sido considerado fundamental para a sobrevivência dos animais, sendo o medo uma se suas mais primitivas e importantes formas. A substância cinzenta periaquedutal dorsal (SCPD) tem-se destacado como uma estrutura importante na organização das respostas defensivas. Estudos usando estimulação elétrica e química da SCPD e microinjeções de drogas agonistas e antagonistas de receptores serotoninérgicos mostraram uma mediação serotoninérgica através dos subtipos de receptores 5-HT1A e 5-HT2A na regulação do comportamento defensivo organizado nesta estrutura. O objetivo deste trabalho foi examinar a mediação serotoninérgica na SCPD através de receptores 5-HT1A nas respostas defensivas de animais sem e com experi~encia aversiva prévia. Para isto, os limiares de congelamento e fuga foram determinados em ratos implantados com uma cânula acoplada a um eletrodo na SCPD, antes e após microinjeção local do agonista 8-OH-DPAT (4 e 8 nmol) e do antagonista WAY100635 (10 nmol). Os efeitos destas drogas injetadas na SCPD foram avaliados também sobre o tempo de congelamento pós-estimulação em animais ingênuos e também em animais colocados em um contexto no qual receberam choques inescapáveis nas patas 24h antes (medo condiconado contextual). O 8-OH-DPAT, de maneira dose dependente, produziu um efeito anti-aversivo sobre os limiares de congelamento e fuga em ratos sem experiência aversiva prévia, mas não nos animais com experiência aversiva prévia quando comparado com seus controles. Por outro lado, este agonista 5-HT1A reduziu o tempo de congelamento contextual. Já o WAY100635 não produziu alterações significativas sobre os limiares aversivos em ratos ingênuos ou com experiência aversiva prévia, mas elevou o tempo de congelamento contextual nestes aniamis (efeito pró-aversivo). Estes resultados estão em concordância com a idéia de uma modulação fásica exercida pela 5-HT sobre os substratos neurais do medo organizado na SCPD. Por outro lado, mecanismos mediados pelos receptores 5-HT1A não são alterados em animais com experiência aversiva prévia. Acreditamos que estes resultados trazem uma contribuição importante para a nossa compreensão sobre a integração de estados aversivos no SNC e, particularmente sobre o funcionamento destes substratos neurais de defesa na SCPD de animais com experiência aversiva prévia. / It is well established that 5-HT1 mechanisms modulate the defensive behavior produced by stimulation of the dorsal periaqueductal gray (dPAG). However, in spite of the notion that past stressful experiences play a role in certain types of anxiety only few studies with stimulation of the dPAG of rats without previous aversive experience have been conducted so far. In this study, we examined the mediation of 5-HT1 receptors of the dPAG in rats naive and in rats previously submitted to contextual fear conditionong (CFC). Defensive behaviors induced by activation of the dPAG were assessed by measuring the lowest intensity of electric current applied to this structure (threshold) able to produce freezing and escape responses during testing sessions of CFC, in which animals were placed in a context previously paired to footshocks. The persistence of the freezing behavior after the interruption of the dPAG electrical stimulation was also evaluated. The 5-HT1 function of the dPAG in this condition was evaluated by local injectinos of 8-OH-DPAT (4 and 8 nmol/) and WAY100635 (10nmol), selective agonist and antagonist of 5-HT1 receptors, respectively. In accordance with previous studies, 8-OH-DPAT increased the aversive thresholds (antiaversive effects) and injection of WAY100635 into the dPAG did not produce significant effects in naive rats. On the contrary, both serotonergic drugs 8-OH-DPAT and WAY100635 did not produce any significant effects on the aversive thresholds. Post-stimulation freezing was not affected by any treatment given to animals before or after CFC. However, the contextual conditioned freezing was attenuated or enhanced by intra-dPAG of 8-OH-DPAT and WAY100635, respectively. The present results suggest that 5-HT1 receptor-mediated mechanisms exert a phasic inhibition on the neural substrates of fear in the dPAG in naive rats whereas past stressful experience does not produce significant changes in the synaptic function of 5-HT1 receptors within the dPAG.

A concepção de aeronaves não convencionais a fim de alcançar um determinado desempenho ou melhoria operacional é sem dúvida um dos objetivos mais importantes da engenheira aeronáutica. Tais melhorias envolvem: redução de arrasto, redução da seção transversal, redução de ruído, redução da distância de decolagem e pouso, aumento da eficiência aerodinâmica, aumento da carga útil, entre outros. Por tanto, métodos de otimização multidisciplinar se tornaram em ferramentas muito úteis para aprimorar o projeto conceitual destas aeronaves. Neste contexto, este trabalho teve como objetivo o desenvolvimento do projeto conceitual de uma aeronave não convencional de combate e a análise de desempenho aerodinâmico do seu sistema de admissão de ar (Intake), tendo como principal característica, estar localizado na parte superior da fuselagem da aeronave (Dorsal Intake). O delineamento conceitual foi desenvolvido através da implementação de metodologias de otimização multidisciplinar de projeto (MDO) na fase de projeto paramétrico, integrando conceitos como: entropia estatística, desdobramento da função qualidade (QFD) e análise de restrições. Além disso, foram usados métodos analíticos e teóricos, ferramentas de desenho assistido por computador (CAD) e simulações da dinâmica dos fluidos computacionais (CFD) para otimizar e obter a configuração final da aeronave. Posteriormente, 5 configurações de asa delta foram selecionadas para avaliar as mudanças de desempenho do dorsal intake sob a influência aerodinâmica das superfícies principais da aeronave (Asa e Fuselagem), em regimes de voo subsônico (Mach = 0.4), transônico (Mach = 0.9) e supersônico (Mach = 1.7; 2) a diversos ângulos de ataque (De α = 10º a α = 30º ). Os resultados encontrados neste trabalho foram avaliados em separado, subsequentemente foram integrados, a fim de obter a nova concepção de aeronave não convencional de combate; a aplicação de MDO permitiu estimar as variáveis de projeto ideais para o desenvolvimento do projeto da aeronave, em relação a sua missão. Em contrapartida, os resultados da integração intake-estrutura mostram que apropriadas características de desempenho e compatibilidade foram mantidas durante as fases de voo subsônicas, para as 5 configurações de asa. No entanto, para velocidades transônicas, a configuração canard apresentou um acréscimo nos níveis de recuperação de pressão total, devido ao fluxo de alta energia na parte superior da fuselagem, o qual é produzido pelo vórtice do canard a moderados ângulos de ataque. Finalmente, para velocidades supersônicas, a asa com dispositivos LEX (Leading Edge Extensions) obteve os melhores níveis de recuperação de pressão total, pois a implementação destes dispositivos apresentou uma montagem mais vantajosa com sua fuselagem para gerar o cone de Mach, aumentando os níveis de recuperação de pressão total e reduzindo a distorção na face do motor. No entanto, para velocidades maiores a Mach = 2, sem importar a configuração de asa, a expansão do escoamento sobre a fuselagem e as asas da aeronave produziu um aumento no número Mach local na entrada do intake, o que reduziu os níveis de desempenho e compatibilidade do mesmo. Em consequência, a posição do intake na parte superior da fuselagem representa uma opção de configuração viável para aeronaves que requerem apenas capacidades de ângulo de ataque razoáveis, tais como aeronaves de caça ar-terra, sendo a asa com dispositivos LEX a geometria que representa melhores qualidades de desempenho na maioria dos 3 regimes de voo avaliados. / The conception of non-conventional aircraft with the aim of achieving a certain performance or operational improvement is undoubtedly, one of the most important objectives of the aeronautical engineering. These improvements involve: drag reduction, cross section reduction, noise reduction, shortening of take-off and landing distance, increase of aerodynamic efficiency, payload increase, among others. Therefore, optimization multidisciplinary methods became in very important tools to upgrade the conceptual design phase of these aircraft. In this context, this work had as aim the development of the conceptual design of a nonconventional fighter aircraft and the aerodynamic performance analysis of its air intake, having as main characteristic to be located at the top of the fuselage (Dorsal Intake). The conceptual design was developed through the implementation of multidisciplinary design optimization (MDO) methods in the parametric design phase, integrating concepts of: statistical entropy, quality function deployment (QFD) and constraint analysis. Besides that, it was used analytical and theoretical methods, computer-aided design (CAD) tools and computational fluid dynamics (CFD) simulations to optimize and obtain the final aircraft configuration. Subsequently, 5 delta wing configurations were selected to evaluate the dorsal intake performance changes under the aerodynamic influence of the main aircraft surfaces (Wings and Fuselage) in subsonic (Mach = 0.4), transonic (Mach = 0.9) and supersonic (Mach = 1.7; 2) flight regimes, at various angles of attack (From α = 10º to α = 30º ). The results found in this work were evaluated separately, later these were integrated, in order to get the new conception of non-conventional fighter aircraft; the MDO application allowed to estimate the ideal design variables for developing the aircraft design, regarding to its mission. On the other hand, the results of the intake-structure integration shown that appropriate performance and compatibility characteristics were maintained during the subsonic flight stages for the 5 wing configurations. However, for transonic velocities, the canard configuration presented an increase in the total pressure recovery levels, due to the high energy flux on the fuselage, which is produced by the canard vortex at moderate angles of attack. Finally, for supersonic velocities, the wing with LEX (Leading Edge Extensions) devices got the best levels of total pressure recovery, because the implementation of these devices presented a more advantageous assembly with its fuselage to generate the Mach cone, increasing the total pressure recovery levels and reducing the distortion at the engine face. However, for velocities higher than Mach = 2, regardless the wing configuration, the flow expansion on the fuselage and the wings produced an increase in the local Mach number in the intake entrance, which reduced the performance and compatibility levels of it. As a consequence, the top mounted intake position represents an option of viable configuration to aircraft that require only reasonable angles of attack capabilities, such as air-to-ground fighter aircraft, being the wing with LEX devices the geometry that represents better performance qualities in the majority of the 3 evaluated flight regimes.

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