Resumo: A síndrome do anticorpo antifosfolípide (SAAF) é caracterizada por tromboses de repetição sendo o acidente vascular cerebral isquêmico (AVCi) uma de suas principais complicações. Os mecanismos da doença cerebrovascular na SAAF não estão totalmente estabelecidos. O objetivo deste estudo foi verificar quais mecanismos poderiam estar envolvidos nesse processo, com ênfase no papel da embolia paradoxal (EP). Métodos: 53 pacientes com SAAF foram avaliados clinicamente e por meio de Doppler transcraniano contrastado (DTCc). Resultados: 23 pacientes com AVCi (grupo AVC) e 30 sem história de AVCi (Grupo controle). Fatores de risco tradicionais para doença cerebrovascular (hipertensão, diabetes, dislipidemia), aterosclerose de grandes vasos e alterações cardíacas não foram diferentes entre os grupos. Também não houve diferença na prevalência de shunt direita esquerda (SDE) entre os grupos. No entanto quando consideramos apenas pacientes com SAAF sem AVCi os escores de testes cognitivos foram melhores em pacientes sem SDE significativo. Conclusões: A EP não parece ser uma causa importante de AVCi em pacientes com SAAF, podendo estar relacionada, no entanto, a outros achados comuns na síndrome como por exemplo déficit cognitivo.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Sono e imunidade parecem apresentar uma relação de reciprocidade. A ativação do sistema imune altera o padrão de sono e distúrbios do sono podem afetar a função imune. Além disso, é bem descrito que a privação de sono paradoxal (PSP) leva à hiperalgesia e o tratamento com fármacos clássicos, como opióides ou antidepressivos tricíclicos, não é capaz de reverter este quadro. Neste trabalho, avaliamos se a PSP afetaria a resposta inflamatória e a sobrevida em ratos e se o tratamento com um análogo sintético de lipoxinas (ATL-1) seria capaz de reverter a hiperalgesia induzida pela PSP. Todos os protocolos experimentais foram previamente aprovados pelo Comitê de Ética para o Uso de Animais, da UERJ (CEUA/032/2010). Ratos Wistar machos foram submetidos a 96 h de PSP, induzidas pelo método de plataforma única (PU) ou de múltiplas plataformas modificado (MPM). Após 96 h de PSP os animais foram submetidos ao modelo da bolha de ar ou pleurisia utilizando-se a carragenina como agente flogístico, ou ainda a PSP foi aplicada antes ou após a indução de um modelo de ligação e perfuração do ceco (CLP). Quatro horas após a injeção de carragenina os animais apresentaram um aumento no recrutamento de leucócitos para a cavidade da bolha, porém não houve diferença entre animais PSP e controles. O número total de leucócitos no plasma não se alterou após a injeção de carragenina. Na pleurisia, os animais PSP apresentaram um aumento nos níveis de IL-6, IL-1β e TNF-α no plasma, enquanto apenas IL-1β e IL-6 estavam aumentados no exsudato pleural dos animais que receberam carragenina. O padrão de recrutamento de leucócitos para o local da injúria foi bastante semelhante entre os animais controle e PSP 2 h, 4 h e 24 h após a injeção de carragenina. Houve um aumento progressivo com o tempo, apresentando um pico em 24 h, no entanto, não foi observada diferença significativa na resposta dos grupos PSP. A PSP aplicada antes ou após a indução do CLP reduziu a sobrevida dos animais, mas não alterou o acúmulo de neutrófilos, nos dois protocolos. Quando a PSP foi aplicada antes do CLP, os níveis séricos de IL-6 estavam aumentados nos grupos PSP e PSPCLP, porém quando a PSP foi aplicada após o CLP, ambas IL-6 e IL-1β estavam aumentadas nos grupo PSPCLP. O efeito do tratamento com ATL-1 (10 g/kg, i.v.) na hiperalgesia induzida pela PSP foi determinado através do teste da formalina. O análogo reduziu o número de comportamentos relacionados à dor em animais PSP e controles na fase inflamatória do teste. Nossos resultados demonstraram que a PSP por 96 h aumentou os níveis plasmáticos de citocinas, reduziu a sobrevida dos animais, contudo não foi capaz de alterar o recrutamento de leucócitos frente a um estímulo inflamatório ou infeccioso. O aumento de mediadores inflamatórios observado nesses animais pode estar relacionado à hiperalgesia em animais PSP, uma vez que o tratamento com o ATL-1 reverteu esse efeito, possivelmente através de mecanismos envolvendo sua ação anti-inflamatória. / Sleep and immunity show a reciprocal relationship. Immune system activation alters sleep pattern and sleep disturbances can affect immune function. Moreover, it is well known that paradoxical sleep deprivation (PSD) leads to hyperalgesia and the treatment with classical drugs like opioids or tricyclic antidepressants is not able to reverse this hyperalgesia. In this work we investigated whether PSD could affect inflammatory response and survival in rats and if ATL-1 treatment would be able to reverse the hyperalgesia induced by PSD. All experimental protocols were previously approved by The Animal Care Ethical Committee of UERJ (CEUA/032/2010). Male Wistar rats were submitted to 96 h of PSD by single platform or modified multiple platforms methods. After 96 h of PSD animals were submitted to carrageenan-induced air pouch or pleurisy, or PSD was induced prior or after cecal ligation and puncture model (CLP). Animals presented an increase in leukocyte recruitment to the pouch cavity 4 h after carrageenan injection, however there was no difference between PSD and controls. The number of plasma leukocyte did not change after carrageenan injection. PSD animals submitted to pleurisy showed an increase in IL-6, IL-1β e TNF-α plasma levels, while IL-1β and IL-6 were increased in pleural exsudate of animals that received carrageenan. Leukocyte recruitment pattern to the site of injury was similar between controls and PSD 2 h, 4 h and 24 h after carrageenan injection. There was a progressive increase with time, reaching the maximum point at 24 h, but no differences were observed in PSD groups. PSD induced prior or after CLP decreased animals survival, however no difference was observed on neutrophil accumulation in both protocols. When PSD was induced prior CLP, IL-6 plasma levels were increased in PSD e PSDCLP groups, when PSD was induced after CLP, IL-6 and IL-1β plasma levels were increased in PSDCLP group. The effect of ATL-1 treatment (10 g/kg, i.v.) on hyperalgesia induced by PSD was determined through formalin test. The treatment reduced the number of pain related behaviors in PSD animals and controls on inflammatory phase. Our results show that ATL-1 was able to revert the hyperalgesia induced by PSD possibly through its anti-inflammatory action. Furthermore, PSD for 96 h increased cytokine plasma levels and reduced survival, however it was not able to modify leukocyte recruitment when challenged by an inflammatory or infectious stimulus. However the inflammatory mediators increase observed in PSD animals could be related to hyperalgesia since treatment with ATL-1 reverted this effect, possibly through anti-inflammatory mechanisms.

Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / A privação de sono paradoxal (PSP) provoca diversas alterações neuroquímicas e comportamentais relacionadas a mudanças nas funções de sistemas de neurotransmissores. São descritas na literatura respostas aumentadas a estímulos álgicos em animais privados desta fase de sono. Os métodos de PSP frequentemente utilizados têm sido associados à geração de ansiedade nos animais, e a hiperalgesia observada poderia, portanto, ser conseqüência aos estímulos ansiogênicos gerados pelo método. Neste trabalho tivemos como objetivos avaliar se o método utilizado para a PSP é ansiogênico e investigar o efeito dos fármacos ansiolítico, diazepam e analgésico, ácido acetilsalicílico sobre a ansiedade e resposta a estímulos térmicos álgicos em animais PSP. Ratos machos Wistar com 90 dias de vida foram privados de sono paradoxal por 96 horas, sendo a resposta álgica avaliada pelo tempo de retirada da pata traseira em ratos expostos à placa quente (46C). A avaliação do nível de ansiedade dos animais foi feita através do teste do campo aberto, através da relação entre a permanência nos quadrantes centrais e nos quadrantes periféricos, e também pelo teste do labirinto em cruz elevado, sendo quantificado o número de vezes que o animal entrava nos braços abertos do labirinto e o tempo gasto pelo animal nos mesmos braços. Os animais PSP apresentaram aumento no índice de locomoção em relação aos animais controles (+314,8%, p<0,05), aumento no número de entradas (+257,1%) e no tempo gasto nos braços abertos do labirinto em cruz elevado (+319,2%, p<0,05), e redução na latência de retirada da pata traseira da placa quente (-64,2%, p<0,05). O fármaco diazepam, não influenciou nas respostas apresentadas pelos animais PSP no teste de campo aberto e no teste da placa quente, mas influenciou nas repostas apresentadas por estes animais no teste do labirinto em cruz elevado tanto no tempo (+308, p<0,05), quanto no número de entradas (+316,6%, p<0,05). O fármaco ácido acetilsalicílico promoveu uma diminuição do índice de locomoção nos animais PSP submetidos ao teste de campo aberto que também foram administrados com o diazepam (-99,5%, p<0,05). No teste da placa quente o ácido acetilsalicílico não apresentou nenhuma influência na percepção de dor nos animais. Os resultados obtidos neste trabalho indicam que o método de privação de sono paradoxal por período de 96 horas não induz ansiedade, e a redução farmacológica dos níveis de ansiedade não influencia na resposta álgica induzida pela privação de sono paradoxal. / Paradoxical sleep deprivation (PSD) causes several neurochemical and behavioral changes related to alterations in neurotransmitters systems. Increased responses to nociceptive stimuli have been reported in animals deprived of this phase of sleep. The commonly used methods of PSD have been linked to the generation of anxiety in animals, and hyperalgesia could, therefore, be due to anxiety stimuli generated by the method. The purpose of this study was to investigate anxiety induced by the PSD method and the effect of the anxiolytic drug diazepam and analgesic drug acetylsalicylic acid on anxiety and response to thermal nociceptive stimuli. Male Wistar rats of 90 days of life were deprived from sleep for 96 hours and submitted to the nociceptive test on the hot plate (46C). The assessment of anxiety level of animals was performed using the open field test, where they made the link between residence in central and peripheral squares, and also by test of the elevated plus maze, whose endpoint was to quantify the number of times that the animal entered in the open arms of the maze and measure the time spent by the animal in the same arms. PSD animals showed increased rate of locomotion compared to control animals (+314.8%, p <0.05), longer time spent in open arms of elevated plus maze (+319.2%, p <0.05), largest number of entries in the same arms of the maze (+257.1%) and reductions in latency to withdraw the hind paw of the hot plate (-64.2%, p <0.05). The drug diazepam, did not influence the responses made by PSD animals in the open field and hot plate test, but influenced the answers given by these animals in test of the elevated plus maze in both time (+308, p <0.05), or the number of entries (+316.6%, p <0.05). The drug acetylsalicylic acid caused a decline in the rate of locomotion in PSD animals subjected to the open field test that also was administered with diazepam (-99.5%, p <0.05). The results of this study indicated that the method of paradoxical sleep deprivation does not appear to be anxiogenic. The results obtained in this work showed that the PSD method does not induce anxiety and the pharmacological reduction in anxiety does not interfere in the increased algic response induced by paradoxical sleep deprivation.

La pratique picturale de He Jaiying nous place face à un paradoxe esthétique : en dépit de sa dimension hétérotopique celle-ci peut-elle être considérée comme une œuvre contemporaine ? Ainsi cette première réflexion nous a –t-elle engagé à interroger la position et le rôle de l’héritage culturel dans les pratiques picturales d’hier et d’aujourd’hui. Nous avons également dû nous intéresser à la question du monde de l’art et de son rapport à une production artistique dite « contemporaine ». Or, en quoi consiste au fond le contemporain ? Le contemporain n’est pas une chose que l’on montre. Il se montre lui-même dans les présences qu’il habite parce qu’il échappe justement à la représentation. De fait, il est une expérience et se vit comme telle. Dans sa quête de spontanéité, nous en faisons l’expérience dans un présent toujours en fuite. De sorte qu’en dehors du temps, ou temps d’entre les temps, il relie les différentes temporalités qui construisent la continuité chronologique. En cela, il n’y a rien de caché. Ou plutôt, ce qui se dissimule dans les œuvres est ce quelque chose que l’on ne voit pas mais à quoi on est sensible. C’est le trouble que nous renvoie la sensation étrange d’un temps hors du temps. Le contemporain est l’expérience que nous faisons du présent dans l’actualité de son événement. C’est un état de suspension. C’est pour cette raison que la présence y prend un caractère total, holiste. Contemporaine au sens où ce qu’elle met en lumière « ne quitte jamais le moment où il naît » (Jean-Luc Nancy), l’œuvre de He Jiaying est un intensificateur de présence et en cela, elle nous rapproche de la sensation absolue d’être-là. / He Jiaying’s pictorial practices leave his viewers with an aesthetic paradox: can his work be considered as contemporary art, despite its heterotypic dimension? A continuity of this initial reflexion from this leading lights of the gongbi artistic genre, leads the viewer to further question the position and the role of cultural heritage in the pictorial practices of today and yesteryears. But what is the link between the world of art and a work of art defined as “contemporary”?What does the contemporary consist of? The contemporary is not something that an artist can show. It reveals itself within the presence it inhabits because it escapes, fittingly, from such representation. It is a de facto experience and is lived as such. In its pursuit for spontaneity, we experience it in the ever-eluding present, so that that it is outside of time, or a time between time, linking different temporalities that make up chronological continuality. In that, nothing is hidden, or more to the point, the thing that is dissimulated in a work of art is that something that we do not see but that we recognise and are sensitive to. It is the discord that gives the viewer that strange feeling of time outside of time. The contemporary is the experience that we have of the present within the actuality of its passing. It’s a state of suspension, and it is for this reason that its presence takes on a total holistic character.Contemporary in the sense of the visible as “it never leaves the moment in which it was born” (Jean-Luc Nancy), the works of He Jiaying is an “intensificator” of presence and therefore, brings us closer to the absolute sensation of just being.

Le sommeil est un état de vigilance présent dans la plupart des espèces animales et impliqué dans de nombreuses fonctions. Le sommeil paradoxal (SP), un des deux stades principaux de sommeil serait étroitement associé à la régulation des émotions. Cette régulation pourrait faciliter la consolidation de la mémoire émotionnelle, et paradoxalement diminuer le tonus émotionnel associé à cette mémoire. Nous proposons que l'hypothèse selon laquelle les premières heures de SP post-apprentissage soient importantes pour la consolidation à très long terme de la mémoire de peur. Pour cela, nous avons effectué un conditionnement de peur au contexte chez la souris suivi de 6h de privation spécifique de SP, et testé la mémoire récente (24 heures) et ancienne (30 jours) des animaux. Notre analyse du comportement révèle une altération spécifique des performances mnésiques des animaux privés de SP lors du rappel de la mémoire ancienne, pointant pour la première fois un rôle du SP post-apprentissage dans la consolidation à très long terme de la mémoire.Nous avons réalisé chez ces animaux une étude immunohistochimique visant à évaluer l'activité des populations neuronales de différentes aires corticales et sous-corticales lors du rappel. Pour cela, nous avons analysé l'expression du gène d'expression précoce zif268. Nos résultats révèlent une importance majeure du SP post-apprentissage dans la mise en place du processus de réorganisation systémique observé lors de la consolidation à très long terme.Nous avons ainsi montré que les premières heures de SP post-apprentissage peuvent être cruciales dans la régulation à très long terme d'une mémoire de la peur. Nous avons également montré que cette fonction du SP passerait par une initialisation précoce de la réorganisation à long terme des réseaux mnésiques, et notamment par une diminution homéostatique de l'activité dans les régions cérébrales impliquées dans l'expression des émotions / Sleep is a vigilance state observed in most of animal species and is involved in many functions. Paradoxical sleep (PS, or Rapid Eye Movement Sleep), an essential sleep state, seems to be closely linked to emotion regulation. It seems that one aspect of this function could be due to the potentiating role of PS in emotional long-term memory, and the paradoxical decrease in the emotional tone associated to the memorized event. We tested the hypothesis that the first hours of post-learning PS could be important for remote long term emotional memory in mice. We performed a contextual fear conditioning followed by 6 hours of PS deprivation, and assessed the memory at recent (24 hours) and remote (30 days) recall. Our behavioral analysis reveals a specific alteration of memory performances when animals were tested at remote delays, revealing for the first time a role of post-learning PS in remote memory consolidation.We then performed immunohistochemistry analysis of neuronal activation during memory recall by assessing the expression of the immediate early gene zif268 in a large number of areas involved in emotional memory processing. Our results reveal a major role of post-learning PS in the regulation of neuronal activity taking place during remote memory consolidation.Thus we show that the first few hours of post-learning PS can be crucial for the regulation remote fear memory. These results suggest that this PS function could be due to the early initialization of remote reorganization of memory networks, acting notably by a homeostatic decrease of neuronal activity in areas involved in the expression of emotions

Selon la théorie du replay, le sommeil améliore la consolidation mnésique des apprentissages récents à travers leur réactivation. Pour tester cette hypothèse, nous avons utilisé le modèle de la somniloquie : les paroles nocturnes reflétant le contenu mental du dormeur et les informations qu’il est en train de traiter. La somniloquie survient fréquemment dans le cadre de parasomnies de sommeil lent (somnambulisme) ou de sommeil paradoxal (TCSP). Nous avons d’abord montré comment ces deux parasomnies correspondaient à la mise en gestes et en paroles du contenu mental du dormeur, avec une prédominance en sommeil lent de rêves de catastrophes que les somnambules fuyaient et en sommeil paradoxal, de rêves d’agressions d’animaux ou de personnes que les patients contre-attaquaient. Ceci soutient le concept de la fonction évolutionniste des rêves comme un entraînement virtuel à « fuir ou combattre » les menaces. Ensuite, nous avons utilisé les somniloquies pour tester si un apprentissage verbal récent était consolidé pendant le sommeil mais aussi si certains mots étaient répétés en dormant. Nous avons d’abord montré que la consolidation mnésique verbale liée au sommeil était bien conservée chez les somnambules comme chez les patients atteints de TCSP, même déments, comparée aux sujets normaux. Ensuite, nous n’avons pas identifié de réexécution de phrases apprises la veille lors des somniloquies de sommeil lent, mais avons identifié chez un patient avec TCSP, un élément sémantique évoquant une réutilisation du contexte de l’histoire. Enfin, nous avons collecté 883 verbatim nocturnes et décrit les aspects acoustico-phonétiques, prosodiques et sémantiques du langage nocturne. / According to the replay theory, sleep improves memory consolidation of recent learning through their reactivation. To test this hypothesis, we used the model of sleep-talking: the words uttered reflecting the mental content of the sleeper and the information he is proceeding. Sleep-talking occur frequently within the context of slow wave sleep (sleepwalking) or REM sleep parasomnias (RBD). We first showed how these two parasomnias corresponded to the setting gestures and words of the mental content of the sleeper, with predominance during slow wave sleep of dreams featuring disasters that sleepwalkers fleeing, and during REM sleep of dreams of attacks by animals or people that subjects counterattack. This supports the concept of evolutionary function of dreams as a virtual drive to “fight or flight” threats. Then, we used sleep-talking to test if a recent verbal was not only consolidated during sleep but also if some words were repeated while sleeping. We first showed that verbal memory consolidation related to sleep was preserved in sleepwalkers as in patients with RBD, even with dementia, compared with normal subjects. Then, we haven’t identified rehearsed sentences of the material learned the day before during slow wave sleep parasomnias, but we identified in a subject with RBD, a semantic component evoking a rehearse of the context of the learned history. Finally, we collected 883 verbatim during sleep and describes the acoustic-phonetic, prosodic and semantic aspects of sleep-talking.

Notre travail interroge l’affinité entre une figure – le paradoxe – et le discours sur les mœurs, tel qu’il s’invente et se développe de Montaigne à La Bruyère : il étudie l’appropriation d’un fait de langue et sa requalification en fait de style. La confrontation des théories existantes sur le paradoxe aux exemples de notre corpus fait apparaître la gradualité de la figure, dont la configuration prototypique connaît des réalisations discursives de forme et d’étendue variables, et dont l’étude stylistique implique l’articulation des points de vue microstructural et macrostructural. En promouvant une approche englobante, continuiste et contextualisée des formes de l’écriture paradoxale, nous soulignons la dimension matricielle du paradoxe, sa propension à constituer, pour les textes que nous étudions, un principe générateur, une forme ordonnatrice : l’étymon d’un style. Nous défendons en effet l’idée selon laquelle le paradoxe constitue un lieu commun de la prose moraliste, c'est-à-dire la forme-sens dans laquelle se cristallisent une éthique et une esthétique, un rapport soupçonneux aux vérités admises et aux discours institués. L’examen des différents usages de la figure et des fonctions qui lui sont dévolues nous permet ainsi d’éclairer les soubassements épistémologiques de l’entreprise moraliste. / Our work reflects upon the affinity between a figure of speech – the paradox – and the moral discourse, as it emerges and evolves from Montaigne to La Bruyère. We study the appropriation of a linguistic form and its revaluation as a stylistic trait. The comparative examination of the theoretical descriptions of the paradox, and their application to our corpus examples reveal the gradualness of the figure, and the variety of its discursive actualizations. By promoting a global, continuist and contextualized approach to the paradox, we stress out its functionality as well as its propensity to shape the reflection and the writing of the classical moralists.

La sérotonine (5-HT) est un neuromodulateur qui joue un rôle essentiel dans la régulation des états de vigilance. Le déséquilibre des taux de sérotonine est impliqué dans l'étiologie des troubles psychiatriques, en particulier des troubles bipolaires et des troubles dépressifs majeurs, qui s'accompagnent également de troubles du sommeil. Basé sur ceci, nous avons émis l’hypothèse selon laquelle une réduction des niveaux de sérotonine devrait perturber le cycle éveil-sommeil. Pour tester cette hypothèse, nous avons utilisé des souris homozygotes (HO) knock-in TPH-2 produisant 20% du niveau normal de sérotonine (Beaulieu et al., 2008) et des souris de type sauvage (WT) avec un taux de sérotonine normal. Dans ces deux groupes, nous avons effectué des enregistrements électrophysiologiques chroniques de l'activité cérébrale dans trois aires corticales (préfrontales, motrices, rétrospléniales) et de l'hippocampe, en plus de l'EMG du cou. Les états de vigilance ont été détectés et la durée de chaque épisode de sommeil et d’éveil a été mesurée. Nous avons constaté que la réduction de sérotonine prolongeait la durée des épisodes de sommeil et de réveil. Les souris HO présentaient un sommeil continu plus long (combinant le sommeil à ondes lentes et le sommeil paradoxal) et des épisodes de réveil plus longs par rapport aux WT. Nous avons également évalué l'activité des ondes lentes dans toutes les zones corticales étudiées et notre étude a révélé que la puissance delta était augmentée chez les souris avec une réduction en sérotonine par rapport aux souris normales. Nous concluons que la réduction des niveaux de sérotonine mène à des états de vigilance plus consolidés. Nos résultats indiquent de manière surprenante que, la sérotonine influence de manière significative l’activité des ondes lentes corticales par augmentation de la puissance du delta. Nos résultats suggèrent également que les humains et les souris réagissent différemment à une réduction du taux de sérotonine. / The serotonin (5-HT) is a neuromodulator that plays a critical role in the regulation of states of vigilance. The disbalance in the levels of serotonin is implicated in the etiology of psychiatric disorders, particularly in bipolar disorder and major depressive disorder, that are also accompanied by sleep disturbances. Based on this, we hypothesized that a reduction in serotonin levels should lead to disruptions in the sleep-wake cycle in mice. To test this hypothesis, we used TPH-2 knock-in homozygote (HO) mice that produce 20% of normal level of serotonin (Beaulieu et al., 2008) and wild-type (WT) mice with normal serotonin level. In both of those groups, we conducted chronic electrophysiological recordings of the brain activity in three (prelimbic, motor, retrosplenial) cortical areas and in the hippocampus in addition to a neck EMG. The states of vigilance were detected, the number and duration of each sleep and wake episode was measured in addition to values of Delta power. We found that the reduction in serotonin levels leads to longer duration and decreased number of individual sleep and wake episodes. HO mice displayed longer continuous sleep (combining slow-wave sleep and REM sleep) and longer wake episodes as compared to WT. We also evaluated the slow-wave activity power in all investigated cortical areas and our study reveal that depletion in serotonin leads to higher values of Delta Power. We conclude that the decrease in serotonin levels cause more consolidated states of vigilance in addition to a reduced number of episodes compared to WT. Our results surprisingly indicate that serotonin significantly influence the cortical slow-wave activity power by increasing Delta power. Our results also suggest that humans and mice differently respond to a reduction in serotonin level.

Les mécanismes neurologiques responsables du déclenchement et de l’homéostasie du sommeil, et du sommeil paradoxal (SP) en particulier, sont l’objet d’un nombre toujours plus important d’études du fait notamment de l’attention croissante portée aux pathologies associées. Les travaux rapportés dans cette thèse s’inscrivent parfaitement dans cette dynamique puisqu’ils ont pour objectif de mieux caractériser les populations neuronales mises en jeu dans la régulation du SP ainsi que leurs interactions. Dans cette optique, nous avons combiné différentes approches techniques complémentaires à savoir : neuroanatomie fonctionnelle, polysomnographie et pharmacologie sur animal libre de se mouvoir. Nous avons ainsi pu démontrer pour la première fois la nature glutamatergique des neurones du SLD, région pontique jouant un rôle central dans la mise en place du SP. De plus, s’il est généralement admis que ces neurones du SLD sont sous le contrôle de neurones GABAergiques situés au niveau de la partie ventrolatérale de la substance grise périaqueducale (VLPAG), le contrôle de ces derniers est encore soumis à controverse. Les résultats que nous avons obtenus suggèrent fortement que l’aire latérale de l’hypothalamus (LH) serait responsable de ce contrôle et donc de celui du SP. En effet, la LH est l’afférence majeure à la VLPAG activée lors d’une hypersomnie de SP. En outre, son inactivation par application locale de muscimol entraine la disparition totale du SP et l’activation des neurones GABAergiques de la VLPAG projetant sur le SLD. En parallèle, nous avons étudié le rôle du noyau réticulé paragigantocellulaire dorsal (DPGi) dans la genèse du SP. Bien que le DPGi fût déjà connu pour être responsable de l’inhibition du locus coeruleus (LC) durant les phases de SP, nous apportons ici un certain nombre d’arguments suggérant que le DPGi pourrait être responsable de l’inhibition, non seulement du LC, mais également de l’ensemble des neurones adrénergiques et noradrénergiques. Cela suggère donc que ce noyau joue également un rôle majeur dans la régulation du SP. Les données rapportées dans cette thèse permettent donc de mieux appréhender les mécanismes neuronaux contrôlant la survenue et la régulation du SP. En particulier, ils apportent de nouvelles données en faveur d’un rôle central de l’hypothalamus dans la régulation du SP puisqu’il constituerait le générateur principal de cet état. / A growing number of studies investigate the neurological mechanisms responsible for paradoxical sleep (PS) genesis and homeostasis. The work presented in this thesis aims to better characterize the neuronal populations implicated in PS regulation and their interrelations. To this purpose, we combined complementary techniques such as functional neuroanatomy, polysomnography and pharmacological approaches on freely moving animals. We thus demonstrated for the first time the glutamatergic nature of SLD neurons which are known to be responsible for muscle atonia and cortical activation characterizing PS. Moreover it is well established that SLD neurons are inhibited by GABAergic cells located inside the ventrolateral part of the periaqueductal gray (VLPAG). Consequently, the control of theses neurons, a crucial step for PS genesis is still a matter of debate. The results we obtained strongly suggest that the lateral hypothalamus (LH) would be responsible for this control and thus for PS. Indeed, LH is the main activated afferent to VLPAG during PS-hypersomnia and its inhibition by muscimol application totally suppresses PS and activates VLPAG GABAergic cells projecting to SLD. We also analyzed the implication of the dorsal part of the paragigantocellular reticular nucleus in PS regulation. Even if it was known that DPGi is responsible for locus coeruleus (LC) inactivation during PS, we brought new evidences showing that DPGi would actually inhibits all noradrenergic and adrenergic cells and not only LC suggesting that DPGi could be of importance for PS genesis. All our data allow us to better understand the PS neuronal network and suggest that, contrary to the classical view that PS is generated by the pons, LH would be the primary PS generator.

Le LPGi est la région bulbaire qui contient le plus grand nombre de neurones exprimant Fos pendant l’hypersomnie de SP. 10% de ces neurones Fos dans le LPGi projettent au locus coereleus, une région SP-Off. Récemment, Sapin et al. ont montré que 70% des neurones exprimant Fos pendant l’hypersomnie de SP sont de nature GABAergique. Notre hypothèse est que le LPGi contient des neurones de nature SP-On dont une partie participerait à l’inhibition des noyaux SP-Off. Nous cherchons à vérifier cette hypothèse, d’autre part à identifier les régions afférentes au LPGi actives au cours du SP et enfin, à identifier les projections du LPGi. Nous avons utilisé l’enregistrement extracellulaire des neurones du LPGi chez le rat vigile en contention stéréotaxique. Nous avons couplé cette technique avec le protocole de privation/ rebond de SP par la technique de la piscine. L’analyse du taux de décharge des neurones enregistrés au sein du LPGi montre que celui-ci contient trois types neuronaux différents (SP-On, SP-Off et indifférents). L’analyse des données neuroanatomiques montre que l’afférence majeure du LPGi, active au cours du SP, réside dans le SLD. Le LPGi est donc bien impliqué dans le réseau du SP car il contient des neurones faisant varier leur taux de décharge avec les différents états de vigilance. Le SLD, considéré comme la structure exécutive du SP, de nature glutamatergique, exciterait le LPGi au cours du SP. Ce dernier, de nature GABAergique, inhiberait le noyau moteur facial. Ce travail met pour la première fois en évidence l’activité de la voie SLD-bulbe rachidien ventrolatéral et suggère que le LPGi participe en partie à l’atonie musculaire caractéristique du SP / The LPGi is a ventrolateral medullary area that contains the highest number of Fos-labelled neurons during a paradoxical sleep (PS) hypersomnia. Ten % of these Fos neurons project to the locus coeruleus, a PS-Off area and 70% of these Fos neurons are GABAergic. Our hypothesis is that the LPGi contains PS-On neurons involved in the inhibition of the PS-Off nuclei. Our aim was to check this hypothesis by recording the unit activity of the LPGi neurons, by identifying the afferent areas to the LPGi and determining its projection areas activated during PS. We have used extracellular unit recordings in the unanethetized head-restrained rat model and coupled this method to a selective PS deprivation using the flower-pot method. The analysis of the firing rate of the LPGi neurons showed that there are three different groups, SP-On, SP-Off and indifferent neurons. Moreover, the SLD, a PS-On area, is the main afferent to the LPGi activated during PS rebound. Our conclusion is that the LPGi is involved in the network generating PS. The SLD, considered as the PS executive area through glutamatergic neurons, may excite the LPGi during this state. The LPGi, through its GABAergic neurons, may inhibit the facial motor nucleus. This work provides for the first time evidence for a SLD-ventrolateral medulla pathway and suggests that the LPGi participates in the muscular atonia occurring during PS