The average funding status for eleven southern state pension plans used by teachers as of 2005 is 86%, which translates into over a $40 billion shortfall. Employing Monte Carlo simulation, this study projects the expected future funding status along with confidence intervals for each of these states over the next 10 years. Projections suggest the average underfunding will remain virtually the same based on current state pension contributions and asset allocations. However, if underlying pension asset returns fail to meet expectations due to high funding risk, the average underfunding could fall to 73%, a shortfall of over $150 billion.

Bergman showed that systems of projections of algebras in a variety will satisfy a certain property if the variety has a near-unanimity term. The converse of this theorem was left open. This paper investigates this open question, and shows that in a locally finite variety, Bergman's Condition implies congruence modularity. / Thesis / Master of Science (MSc)

Lyme disease is a common tick borne disease in the US. Lyme disease emerged from the Northeast and in the past decade, Virginia has been witnessing a rapidly increasing trend in incidence. This thesis uses land cover projection data as a basis to look at the potential future trend of Lyme disease incidence in Virginia for the IPCC (Intergovernmental Panel on Climate change) scenarios of A1B and A2, which indicate a global and regional focus respectively. This study is a continuation of previous work done by an NSF funded research team at Virginia Tech, in exploring the variables affecting Lyme disease in Virginia. A Poisson point process is implemented in this thesis with land cover parameters (implemented land, water bodies, and edge metrics) and demographic parameters (population percentage and per capita income) as the spatial covariates. Lyme disease incidence data obtained from the Virginia Department of Health was used for model validation. The overall model was implemented using Python and its associated libraries while ArcGIS software was used for preliminary covariate analysis and data visualization. This thesis generates risk maps for A1B and A2 scenarios for each decade from 2010 through 2060. Spatial occurrence of disease incidence has been generated by the Poisson point process and the risk level of each county in Virginia has been calculated based on the incidence count predicted for it. Population and area at risk under each scenario for each decade was calculated. Results show that in A1B scenario 22.1% and 42.9% of the total population of Virginia are under high risk and in the A2 scenario, 21% and 33% of the total population of Virginia are under high risk of Lyme disease in 2010 and 2060 respectively. In terms of the area, A1B scenario has 28% under high risk in 2010 and 66% of the total area under high risk in 2060, while A2 scenarGIS, Lyme disease, Land cover projections, IPCC scenariosio has 22.4% under high risk of Lyme disease in 2010 62.7% of the total area in Virginia is under high risk in 2060. / Master of Science

As técnicas de projeção multidimensional tornaram-se uma ferramenta de análise importante. Elas buscam mapear dados de um espaço multidimensional para um espaço visual, de menor dimensão, preservando as estruturas de distância ou de vizinhança no mapa visual produzido. Apesar dos recentes avanços, as técnicas existentes ainda apresentam deficiências que prejudicam a sua utilização como ferramentas exploratórias em certos domínios. Um exemplo está nos cenários streaming, nos quais os dados são produzidos e/ou coletados de forma contínua. Como a maioria das técnicas de projeção necessitam percorrer os dados mais de uma vez para produzir um layout final, e fluxos normalmente não podem ser carregados por completo em memória principal, a aplicação direta ou mesmo a adaptação das técnicas existentes em tais cenários é inviável. Nessa tese de doutorado é apresentado um novo modelo de projeção, chamado de Xtreaming, no qual as instâncias de dados são visitadas apenas uma vez durante o processo de projeção. Esse modelo é capaz de se adaptar a mudanças nos dados conforme eles são recebidos, atualizando o mapa visual para refletir as novas estruturas que surgem ao longo do tempo. Os resultados dos testes mostram que o Xtreaming é muito competitivo em termos de preservação de distâncias e tempo de execução se comparado com técnicas do estado-da-arte. Também é apresentada uma nova técnica de projeção multidimensional, chamada de User-assisted Projection Technique for Distance Information (UPDis), que foi projetada para permitir a intervenção do usuário exigindo apenas informações de distância entre as instâncias, e que é utilizada como parte do Xtreaming. Os resultados também mostram que a UPDis é tão rápida, precisa e flexível quanto as técnicas do estado-da-arte. / Multidimensional Projection techniques have become an important analytics tool. They map data from a multidimensional space into a visual space preserving the distance or neighborhood structures on the produced layout. Despite the recent advances, existing techniques still present drawbacks that impair their use as exploratory tools on certain domains. An example is the streaming scenario, in which data are captured or produced continuously. Since most projection techniques need to traverse the data more than once to produce a final layout, and streaming data typically cannot be completely loaded into the main memory, the direct use or even adaptation of the existing techniques in such scenarios is infeasible. In this dissertation, we present a novel projection model, called Xtreaming, wherein the data instances are visited only once during the projection process. This model is able to adapt itself to the changes in data as data is received, updating the visual layout to reflect the new structures that emerge over time. The tests show that Xtreaming is very competitive regarding distance preservation and running time when compared with state-of-the-art projection techniques. We also present a new multidimensional projection technique, called User-assisted Projection Technique for Distance Information (UPDis), that was designed to allow user intervention requiring only distance information between data instances. UPDis is used as part of the Xtreaming model. The results show that UPDis is as fast, accurate and flexible as state-of-the-art techniques.

Devenue une question de santé publique, la grande prématurité pose des questions éthiques, médicales et psychologiques. Considérée comme un facteur de risque de maltraitance et de troubles du spectre autistique, la littérature scientifique met en avant les effets du traumatisme pour expliquer la difficulté de nouage des liens précoces entre la mère et son enfant. A partir de l’analyse discursive et thématique de 34 entretiens de recherches menés avec 15 femmes primipares dans le cadre d’une recherche longitudinale et comparative, la construction du maternel et le rapport subjectif à la médicalisation et au discours des professionnels de soin rencontrés ont été explorés. Les résultats mettent en lumière l’effet loupe que permet les naissances très prématurées sur la construction du processus de maternalité en dévoilant, à travers le décalage entre la naissance physique et psychique, l’importance de la libidinisation ou de la phallicisation du bébé prématuré dans la création du lien. Ils éclairent également la spécificité de ce contexte de naissance à travers la place que prend cet « autre » qu’est la médecine dans ces naissances dont la survie de l’enfant dépend de sa technique. / As a public health issue, extreme premature birth raises ethical, medical and psychological issues. Considered as a risk factor for child maltreatment and autism spectrum disorders, scientific literature puts forward the effects of trauma to explain the difficulty of forming early ties between the mother and her child. From the discursive and thematic analysis of 34 research interviews conducted with 15 primiparous women in the framework of a longitudinal and comparative research, the construction of the maternal and the subjective relationship to medicalization and the rhetoric of healthcare professionals met were explored. The results highlight the magnifying effect that very premature births can have on the construction of the maternal process by revealing, via the gap between physical and psychic birth, the importance of the libidinisation or phallicisation of the premature baby in the establishment of the relationship. They also shed light on this unique birth context by revealing the place that the “other” represented by medicine holds in such births for which the survival of the child depends on its skills.

Malgré des conditions sèches qui prédominent depuis les années 1970, l’Afrique de l’Ouest a subi au cours des deux dernières décennies des épisodes d’inondations sévères qui ont provoqué de nombreux décès et dommages socio-économiques. L’émergence de ce nouveau problème montre une nouvelle facette de la sensibilité de cette région aux changements hydro-climatiques, appelant à une meilleure caractérisation de l’aléa inondation, des processus qui le génèrent, ainsi que la mise en place de méthodes permettant de projeter les évolutions futures de cet aléa pour mieux s’en prémunir.Dans ce contexte, la thèse cherche à répondre à trois questions principales :1) L’augmentation des dommages liés aux inondations s’est-elle accompagnée d’une intensification des crues extrêmes en Afrique de l’Ouest?2) Comment modéliser les orages de mousson, premier facteur de génération du ruissellement, afin d’explorer l’impact de leurs caractéristiques sur les crues?3) Compte tenu des changements climatiques à l’œuvre dans la région, à quelles tendances hydro-climatiques peut-on s’attendre dans le futur ?Dans un premier temps, on évalue l’évolution des crues en Afrique de l’Ouest au cours des soixante dernières années en utilisant de méthodes basées sur la théorie de valeurs extrêmes. Les résultats montrent une augmentation forte des événements hydrologiques extrêmes depuis les années 1970s dans les sous-bassins Sahéliens du fleuve Niger et depuis les années 1980s dans les sous-bassins soudano-guinéens du fleuve Sénégal. Les niveaux de retour calculés à partir des modèles non-stationnaires dépassent ceux qui ont été calculés avec un modèle stationnaire avec plus de 95% de certitude pour les périodes de retour les plus courtes (<10 ans).On présente ensuite des développements récents apportés à un simulateur stochastique d’orages de mousson à meso-échelle (StochaStorm). Ils incluent: une modélisation de l’occurrence de ces orages, la représentation explicite des valeurs de pluie extrêmes et une amélioration du schéma temporel d’intensité infra-événementielle. Implémenté et évalué à partir des donnés haute-résolution de l’observatoire AMMA-CATCH, le générateur montrent de très bonnes capacités à reproduire les propriétés des orages, confirmant son potentiel pour des études d’impact hydrologique.Enfin, une chaîne de modélisation est élaborée afin de proposer des projections hydrologiques pour le futur sur un bassin sahélien de meso-échelle (Dargol, 7000 km²). L’originalité de cette chaîne provient de la prise en compte du continuum d’échelles entre climat global et impact local à travers la représentation du régime des pluies à l’échelle des orages de mousson, dont les propriétés d’occurrence et d’intensité ont des impacts majeurs sur la réponse hydrologique. La chaîne de modélisation inclut le modèle climatique CP4-Africa, unique modèle à convection explicite fournissant des simulations de long terme en Afrique ; une méthode de débiaisage statistique; le simulateur Stochastorm ; et un modèle pluie-débit spécifiquement adapté aux processus hydrologique sahéliens. La chaine est évaluée sur une période de contrôle 1997-2006 puis utilisée pour des projections futures montrant une hausse par un facteur 1,5 des débits maximum annuels et un doublement des volumes moyens annuels à l’horizon 2100.Les résultats ont des implications majeures notamment pour l’ingénierie hydrologique. Les méthodes actuellement utilisées pour appréhender les risques hydrologiques dans la région ne prennent pas en compte la non-stationnarité hydro-climatique risquant de sous-évaluer l’aléa hydrologique et sous-dimensionner les ouvrages hydrauliques utilisés pour s’en protéger. La thèse suggère aussi quelques pistes afin mieux définir les trajectoires hydrologiques passées et futures en incluant, au-delà des précipitations, les changements sociétaux et environnementaux, leurs interactions et rétroactions dans les approches de modélisation. / The semi-arid regions of West Africa are known for their dry conditions which have predominated since the 1970s. In recent years, however, West Africa has witnessed a series of severe flooding events which caused widespread fatalities and socioeconomic damages. The emergence of this new problem demonstrates the sensitivity of the region to changes in the hydroclimatic system and calls for an improved characterization of flood hazard and the mechanisms that generate it. It also signals the need to develop projections for how flood hazard may evolve in the future in order to inform appropriate adaptation measures.In this context, the following PhD thesis seeks to answer three main questions:1) Is there a significant trend in extreme streamflow in West Africa, or are the documented flooding events isolated incidences?2) How can one model mesoscale convective systems, the primary driver of runoff in the region, in order to explore the properties of precipitation that drive streamflow?3) Based on potential climate change in the region, what trends might be observed in streamflow in the future?First, changes in extreme hydrological events West Africa over the past 60 years are evaluated by applying non-stationary methods based on extreme value theory. Results show a strong increasing trend in extreme hydrological events since the 1970s in the Sahelian Niger River basin and since the 1980s in the Sudano-Guinean catchments in the Senegal River basin. Return levels calculated from non-stationary models are determined to exceed those calculated from a stationary model with over 95% certainty for shorter return periods (<10 years).Next, recent developments are presented for a stochastic precipitation simulator (Stochastorm) designed for modeling mesoscale convective storms, the main rainfall source in the Sahel. Developments include a model for storm occurrence, the explicit representation of extreme rainfall values, and an improvement in the modeling of sub-event intensities. Using high-resolution data from the AMMA-CATCH observatory, simulation outputs were confirmed to realistically represent key characteristics of MCSs, showing the simulator’s potential for use in impact studies.Finally, a modeling chain for producing future hydrological projections is developed and implemented in a Sahelian river basin (Dargol, 7000km2). The chain is original as it is the first attempt in West Africa to encompass the continuum of scales from global climate to convective storms, whose properties have major impacts on hydrological response and as a result local flood risk. The modeling chain components include the convection-permitting regional climate model (RCM) CP4-Africa, the only RCM (to date) explicitly resolving convection and providing long-term simulations in Africa; a bias correction approach; the stochastic precipitation generator Stochastorm; and a rainfall-runoff model specifically developed for Sahelian hydrological processes. The modeling chain is evaluated for a control period (1997-2006) then for future projections (ten years at the end of the 21st century). Hydrological projections show that peak annual flow may become 1.5-2 times greater and streamflow volumes may double or triple on average near the end of the 21st century compared to 1997-2006 in response to projected changes in precipitation.The results raise critical issues notably for hydrological engineering. Current methods used to evaluate flood risk in the region do not take non-stationarity into account, leading to a major risk of underestimating potential floods and undersizing the hydraulic infrastructure designed for protecting against them. It is also suggested to not only consider rainfall changes but also societal and environmental changes, interactions, and feedbacks in order to better attribute past hydrological hazards and their future trajectories to related causes.

Les cellules ganglionnaires de la rétine (CGR) projettent dans le corps genouillé latéral dorsal (CGLd) et le colliculus supérieur (CS). Initialement, les projections établissent des connexions imprécises avec les cibles puis elles se raffinent grâce à des mécanismes activité-dépendant. D’abord, j’ai cherché à déterminer la contribution de la libération synaptique dans le raffinement des cartes visuelles en utilisant un modèle où Rim 1 et 2, protéines essentielles à la libération synaptique calcium-dépendante, sont délétées dans les CGRs. J’ai montré que la libération synaptique était nécessaire à la ségrégation œil spécifique dans le CGLd mais pas dans le CS, qu’elle était impliquée dans le raffinement de la topographie de la projection ipsilatérale mais qu’elle n’était pas impliquée dans la rétinotopie des projections controlatérales dans le CS. Ensuite, j’ai cherché à identifier un microdomaine de signalisation AMPc au niveau des cônes de croissance impliqué dans le raffinement des projections rétiniennes. La compartimentation spatiale des signaux AMPc pourrait expliquer qu’ils soient capables de réguler des voies de signalisation distinctes de façon spécifique. J’ai montré que la perturbation des signaux AMPc dans les radeaux lipidiques entraine des défauts de raffinement des projections dans le CS tandis que leur perturbation à la membrane mais en dehors des radeaux lipidiques n’entraine pas de défauts. J’ai aussi montré que la perturbation de la signalisation AMPc dans une petite fraction de CGRs d’un œil suffit à perturber largement la carte œil spécifique, suggérant une coopération entre les projections nécessaire à leur raffinement. / Retinal ganglion cells (RGCs) project to the dorsal lateral geniculate nucleus (dLGN) and to the superior colliculus (SC). Initially, retinal projections establish imprecise connections with the target cells then refine through activity-dependent mechanisms.First, I studied the role of synaptic release in the visual maps refinement, using a mouse model where Rim 1 and 2, which are proteins important for calcium-dependent synaptic release, are deleted in the RGCs. I found that synaptic release is important for eye specific segregation in the dLGN but not in the SC, that it is involved in the refinement of the ipsilateral projection topography but that it is not involved in the contralateral projection retinotopy in the SC.Second, I identified a microdomain of cAMP signaling in growth cones involved in the refinement of retinal projections. The spatial compartmentation of cAMP signals could explain the fact that cAMP signals are able to regulate specifically different signaling pathways. I found that cAMP signals perturbation within the lipid rafts of the RGCs induces defects in the refinement of retinal projections in the SC while their perturbation at the membrane level but outside the lipid rafts does not induce defects.I also showed that cAMP signaling perturbation only in a fraction of RGCs in one eye is sufficient to extensively disturb the eye specific map, suggesting that a cooperation between the projections is necessary for their refinement.

As técnicas de projeção multidimensional tornaram-se uma ferramenta de análise importante. Elas buscam mapear dados de um espaço multidimensional para um espaço visual, de menor dimensão, preservando as estruturas de distância ou de vizinhança no mapa visual produzido. Apesar dos recentes avanços, as técnicas existentes ainda apresentam deficiências que prejudicam a sua utilização como ferramentas exploratórias em certos domínios. Um exemplo está nos cenários streaming, nos quais os dados são produzidos e/ou coletados de forma contínua. Como a maioria das técnicas de projeção necessitam percorrer os dados mais de uma vez para produzir um layout final, e fluxos normalmente não podem ser carregados por completo em memória principal, a aplicação direta ou mesmo a adaptação das técnicas existentes em tais cenários é inviável. Nessa tese de doutorado é apresentado um novo modelo de projeção, chamado de Xtreaming, no qual as instâncias de dados são visitadas apenas uma vez durante o processo de projeção. Esse modelo é capaz de se adaptar a mudanças nos dados conforme eles são recebidos, atualizando o mapa visual para refletir as novas estruturas que surgem ao longo do tempo. Os resultados dos testes mostram que o Xtreaming é muito competitivo em termos de preservação de distâncias e tempo de execução se comparado com técnicas do estado-da-arte. Também é apresentada uma nova técnica de projeção multidimensional, chamada de User-assisted Projection Technique for Distance Information (UPDis), que foi projetada para permitir a intervenção do usuário exigindo apenas informações de distância entre as instâncias, e que é utilizada como parte do Xtreaming. Os resultados também mostram que a UPDis é tão rápida, precisa e flexível quanto as técnicas do estado-da-arte. / Multidimensional Projection techniques have become an important analytics tool. They map data from a multidimensional space into a visual space preserving the distance or neighborhood structures on the produced layout. Despite the recent advances, existing techniques still present drawbacks that impair their use as exploratory tools on certain domains. An example is the streaming scenario, in which data are captured or produced continuously. Since most projection techniques need to traverse the data more than once to produce a final layout, and streaming data typically cannot be completely loaded into the main memory, the direct use or even adaptation of the existing techniques in such scenarios is infeasible. In this dissertation, we present a novel projection model, called Xtreaming, wherein the data instances are visited only once during the projection process. This model is able to adapt itself to the changes in data as data is received, updating the visual layout to reflect the new structures that emerge over time. The tests show that Xtreaming is very competitive regarding distance preservation and running time when compared with state-of-the-art projection techniques. We also present a new multidimensional projection technique, called User-assisted Projection Technique for Distance Information (UPDis), that was designed to allow user intervention requiring only distance information between data instances. UPDis is used as part of the Xtreaming model. The results show that UPDis is as fast, accurate and flexible as state-of-the-art techniques.

Il existe plusieurs filtrations intéressantes définies sur la sous-algèbre de Cartan d'une algèbre de Lie simple complexe issues de contextes très variés : l'une est la filtration principale qui provient du dual de Langlands, une autre provient de l'algèbre de Clifford associée à une forme bilinéaire invariante non-dégénérée, une autre encore provient de l'algèbre symétrique et la projection de Chevalley, deux autres enfin proviennent de l'algèbre enveloppante et des projections de Harish-Chandra. Il est connu que toutes ces filtrations coïncident. Ceci résulte des travaux de Rohr, Joseph et Alekseev-Moreau. La relation remarquable entre les filtrations principale et de Clifford fut essentiellement conjecturée par Kostant. L'objectif de ce mémoire de thèse est de proposer une nouvelle démonstration de l'égalité entre les filtrations symétrique et enveloppante pour une algèbre de Lie simple de type A ou C. Conjointement au résultat et Rohr et le théorème d'Alekseev-Moreau, ceci fournit une nouvelle démonstration de la conjecture de Kostant, c'est-à-dire une nouvelle démonstration du théorème de Joseph. Notre démonstration est très différentes de la sienne. Le point clé est d'utiliser une description explicite des invariants via la représentation standard, ce qui est possible en types A et C. Nous décrivons alors les images de leurs différentielles en termes d'objects combinatoires, appelés des chemins pondérés, dans le graphe cristallin de la représentation standard. Les démonstrations pour les types A et C sont assez similaires, mais ne nouveaux phénomènes apparaissent en type C, ce qui rend la démonstration nettement plus délicate dans ce cas. / There are several interesting filtrations on the Cartan subalgebra of a complex simple Lie algebra coming from very different contexts: one is the principal filtration coming from the Langlands dual, one is coming from the Clifford algebra associated with a non-degenerate invariant bilinear form, one is coming from the symmetric algebra and the Chevalley projection, and two other ones are coming from the enveloping algebra and Harish-Chandra projections. It is known that all these filtrations coincide. This results from a combination of works of several authors (Rohr, Joseph, Alekseev-Moreau). The remarkable connection between the principal filtration and the Clifford filtration was essentially conjectured by Kostant. The purpose of this thesis is to establish a new correspondence between the enveloping filtration and the symmetric filtration for a simple Lie algebra of type A or C. Together with Rohr's result and Alekseev-Moreau theorem, this provides another proof of Kostant's conjecture for these types, that is, a new proof of Joseph's theorem. Our proof is very different from his approach. The starting point is to use an explicit description of invariants via the standard representation which is possible in types A and C. Then we describe the images of their differentials by the generalised Chevalley and Harish-Chandra projections in term of combinatorial objects, called weighted paths, in the crystal graph of the standard representation. The proofs for types A and C are quite similar, but there are new phenomenons in type C which makes the proof much more tricky in this case.

La transmission des messages douloureux depuis les nocicepteurs périphériques jusqu’aux structures supraspinales est sous le contrôle de systèmes modulateurs, parmi lesquels figurent les voies bulbo-spinales sérotoninergiques. Cependant leur rôle n’est pas complètement élucidé puisque selon le type de récepteur sérotoninergique mis en jeu, elles pourraient soit réduire la sensation douloureuse soit au contraire l’exacerber. De plus, le contrôle exercé par la sérotonine (5 HT) pourrait dépendre du type de douleur, aiguë, inflammatoire ou neuropathique chronique. En réalité, ces ambiguïtés tiennent au fait que les études réalisées jusqu’à présent ont surtout impliqué des approches pharmacologiques souvent peu fiables. Ce constat m’a conduit à mettre en œuvre une nouvelle approche expérimentale pour tenter de cerner le véritable rôle modulateur des voies sérotoninergiques bulbo-spinales sur différents types de douleur dans des conditions physiologiques normales ou physiopathologiques chez le rat. A cette fin, j’ai réalisé ce travail de thèse en trois étapes. La première étape a consisté à préciser les caractéristiques anatomiques des voies sérotoninergiques bulbo-spinales visualisées par un marquage antérograde (PHA-L) couplé à l’immunomarquage du transporteur de la sérotonine (SERT). L’étude différentielle des deux sous-structures de la région bulbaire B3 : le noyau raphé magnus (RMg) et le noyau paragigantocellulaire latéral (LPGi) m’a permis de montrer que les neurones sérotoninergiques qu’elles contiennent se projettent respectivement dans les couches profondes (VI-VI) et superficielles (I-II) de la corne dorsale, à tous les étages de la moelle épinière. Afin de dépléter sélectivement la 5-HT dans la corne dorsale, j’ai, dans une deuxième étape, injecté bilatéralement dans la région B3 un lentivirus recombinant LV-shTPH2 pour y éteindre l’expression de la TPH2, l’enzyme limitante de la synthèse de 5-HT. Les contrôles immunohistochimiques ont montré l’inhibition bilatérale de l’expression de la TPH2 dans le RMg et le LPGi, et la diminution de l’immunomarquage de la 5-HT sélectivement dans la corne dorsale, l’expression inchangée du transporteur SERT confirmant le maintien de l’intégrité des fibres sérotoninergiques chez les rats LV-shTPH2. L’évaluation de la sensibilité des animaux ainsi déplétés en 5-HT à différents tests validés de nociception aiguë n’a pas révélé de modifications significatives par rapport aux témoins. Mais dans des conditions de forte stimulation nociceptive thermique (50°C) ou chimique (carragénine), l’augmentation de l’immunomarquage de c-Fos dans la corne dorsale chez les rats LV-shTPH2 montre que la déplétion de 5-HT facilite la sensibilisation synaptique. Des différences encore plus nettes entre les rats LV-shTPH2 et les témoins sont surtout apparues en cas de douleur inflammatoire (formaline) ou neuropathique (ligature du nerf sciatique). Les modifications induites par la déplétion de 5-HT n’étaient cependant pas univoques puisqu’une hypoalgésie a été observée dans le cas d’une douleur inflammatoire et, qu’au contraire, l’hyperalgésie associée à la douleur neuropathique était exacerbée chez les rats LV-shTPH2. Ces modulations opposées laissant à penser l’implication de projections et/ou de récepteurs sérotoninergiques distincts, nous avons réalisé, dans une troisième étape, une étude pharmacologique qui a permis de montrer que l’effet pro-hyperalgésique observé chez les rats neuropathiques déplétés en 5-HT était probablement lié à un déficit d’activation de récepteurs 5 HT7. Notre étude démontre la réalité du contrôle physiologique du relai spinal des voies nociceptives par la 5-HT, via l’implication de projections bulbo-spinales et de récepteurs sérotoninergiques dont l’identification pourrait déboucher sur de nouvelles perspectives thérapeutiques. / The transmission of pain signals from peripheral nociceptors to supraspinal structures is under the control of modulatory systems, which include bulbo-spinal serotoninergic pathways. However, their role is not yet fully understood, as they may as well reduce or exacerbate pain as a function of 5-HT receptor types involved. Furthermore, their modulatory role might also differ depending on whether pain is acute, or chronic, with inflammatory or neuropathic origin. In fact, this ambiguous knowledge results from data essentially obtained with rather unreliable pharmacological approaches. This led me to set up an innovative experimental approach for a better assessment of the real implication of bulbo-spinal serotoninergic projections in pain control mechanisms under validated physiological and pathophysiological conditions in the rat. To this goal, I performed my PhD thesis work in three steps. The first step consisted of a precise anatomical description of bulbo-spinal serotoninergic projections identified by anterograde labeling (with PHA-L) and immunolabeling of the 5-HT transporter (SERT). The differential labeling of the two sub-areas within the B3 bulbar region : the nucleus raphé magnus (RMg) and the nucleus paragigantocellularis lateralis (LPGi) allowed the demonstration that their respective 5-HT neuron groups project separately into the deep (V-VI) and superficial (I-II) laminae of the dorsal horn, at all levels of the spinal cord. For the second step, aimed at depleting 5-HT selectively within the dorsal horn, I injected bilaterally into the B3 area a recombinant lentivirus, LV-shTPH2, designed to suppress the expression of TPH2, the rate limiting enzyme for 5-HT synthesis. Immunohistochemical controls showed that the resulting bilateral inhibition of TPH2 expression in both the RMg and the LPGi was associated with 5-HT depletion but no change in SERT (as expected of unaltered 5-HT fibers) in the dorsal horn. Using various behavioral tests, I could not detect any change in acute pain sensitivity in 5-HT-depleted rats. In contrast, the increased c-Fos immunohistochemical labeling within the dorsal horn after strong thermal (50°C) or chemical (carrageenan) noxious stimulation showed that 5-HT depletion promotes synaptic sensitization. Even more striking differences between LV-shTPH2 injected rats and paired controls were observed in case of inflammatory (formalin) or neuropathic (sciatic nerve ligation) pain. However, 5-HT depletion-induced changes differed under both conditions since hypoalgesia was noted in case of inflammatory pain, whereas neuropathic pain-evoked hyperalgesia was enhanced in 5-HT depleted, LV-shTPH2-injected rats. Because such opposite modulations might have been underlain by distinct serotoninergic pathways (i.e. from the RMg versus the LPGi for instance) and/or distinct 5-HT receptors, we decided, within the time remaining for achieving my PhD work, to perform a third step, focused on the 5-HT7 receptor type. Using pharmacological approaches, we could obtain data showing that exacerbated hyperalgesia in 5-HT-depleted neuropathic rats resulted from loss of tonic 5-HT7 receptor activation by endogenous 5-HT. Altogether, our data clearly demonstrate that bulbospinal serotoninergic projections are involved in the physiological control of pain signaling at spinal cord level. Further identification of underlying neuronal pathways and receptors might open novel therapeutic perspectives.