Early-life stress, consisting of several stressors appears to be associated with several impacts on the brain. The impacts of stress seem to be more vulnerable to the developing brain as it undergoes important changes during childhood. This thesis aims to present the association between childhood maltreatment, which is a form of early-life stress, and affected brain regions such as the hippocampus, prefrontal cortex, corpus callosum, and the amygdala. The findings in this thesis demonstrated the left hippocampus to be more vulnerable to the effects of maltreatment, corpus callosum appeared to be gender and maltreatment specific, indicating that the corpus callosum were more vulnerable to neglect in boys whereas in females the structure was more vulnerable to sexual abuse. The prefrontal cortex demonstrated a marked reduction in gray matter, and the amygdala showed increased activation in response to emotional facial expressions. Cognitive deficits as a result of earlylife stress were also discussed, showing that worse intellectual ability and the academic performance had been noted in children with exposure to early-life stress.

In the field of neuroscience, being in love and feeling romantically attached to a partner is described as a dynamic process. Romantic love may be viewed as a motivational system, changing throughout time and place, fluctuating on the interest and motivation of the individual. Early memories and attachment towards a caregiver, lay the foundation for later attachment behavior, also known as attachment styles. In this thesis, an exploratory approach is present. The thesis aims to introduce and describe the neural correlates of romantic love and romantic attachment. Brain regions concerned with reward, emotion and thought processing, such as the reward circuitry network of the brain and the limbic system, are being investigated. So are other brain areas involved in romantic love and romantic attachment. Research findings suggest that brain areas responsible for affection, emotional control, learning, memory and social judgment are all involved in the complex processes of being in love and feeling romantically attached. These findings are represented by the involvement of the frontal lobe, cerebral cortex, limbic system, orbitofrontal cortex, and hippocampus, anterior cingulate cortex (ACC), ventral tegmental area (VTA), caudate tail, including the reward pathways of the brain. Distribution and regulation of neurotransmitters such as; vasopressin, oxytocin, dopamine, corticosterone and serotonin are all present in the state of romantic  attachment and romantic love. Overlapping evidence confirms the involvement of the reward circuitry network, together with the limbic system as crucial in the formation and maintenance of a romantic relationship.

Nous avons démontré la présence d'apoptose dans le système limbique suivant un infarctus du myocarde. Cette mort cellulaire serait partiellement reliée à l'augmentation de cytokines pro-inflammatoires. Des études démontrent que certains probiotiques ont des effets bénéfiques en diminuant le ratio de cytokines pro/anti-inflammatoires. La prise de probiotiques en prévention, avant l’occlusion d’une artère coronarienne, pourrait-elle diminuer l’apoptose dans le système limbique? Méthodes : La combinaison de probiotiques Lactobacillus helveticus R0052 et Bifidobacterium longum R0175 ou son véhicule fut additionné dans l’eau des rats pendant 28 jours consécutifs. Un infarctus du myocarde fut provoqué par l’occlusion de l’artère coronaire gauche. Après 40 minutes d'occlusion, les régions ischémiques ont été reperfusées pour 72 heures. Les animaux furent sacrifiés et la taille de l'infarctus mesurée. L'amygdale et l'hippocampe furent prélevés pour déterminer l'activité de la caspase-3 (pro-apoptotique), le ratio Bax/Bcl2(proapoptotique/ anti-apoptotique) et l'activité d'Akt (survie cellulaire). Résultats : La taille de l’infarctus n'est pas diminuée dans le groupe probiotique (45% de la région à risque)comparé au groupe placebo. Nos marqueurs d’apoptose démontrent une diminution dans les régions du gyrus denté, de l’amygdale latérale et médiane dans le groupe probiotique par rapport au placebo. L’activité de la caspase-3 et le ratio Bax:Bcl2 furent réduits dans le groupe probiotique de 50% et 40% respectivement (p < 0.05) et phosphorylation d’Akt fut augmentée de 35% (p<0.05). Aucune différence fut observée pour les régions Ca1 et Ca3. Conclusion : La combinaison de probiotiques utilisée réduit l’apoptose dans différentes régions du système limbique 72 heures après un IM. / Apoptosis is observed in limbic system after a myocardial infarction (MI). This cell death is due to the release of pro-inflammatory cytokines. Since probiotics reduce the pro/anti-inflammatory cytokine ratio, we hypothesise that probiotics will lessen apoptosis in the limbic system following MI. Methods: Rats were given probiotics or placebo for 4 consecutive weeks. Rat in the probiotic group received a daily dose of over 1 billion live bacterial cells of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 in combination. A MI was then induced in anesthetised rats by a 40-minute occlusion of the left anterior coronary artery followed by a 72 hours of reperfusion. Infarct size was measured and apoptosis was determined in the amygdala and hippocampus in both groups. Results: Infarct size was not diminished in the probiotic group (45% of the risk area), apoptosis was lessened in the dentate gyrus (DG), the lateral (LA) and medial (MA)amygdala compared to the placebo group. Caspase-3 and Bax/Bcl2 ratio were reduced in the probiotic group by about 50% and 40% respectively. Akt activity was increased by 35% in these regions. No difference was observed in the hippocampus Ca1 and Ca3 regions. Conclusion: This probiotic combination can reduce the apoptosis found in specific regions of the limbic system following a MI, which may have significance for post-MI depression.

Au niveau clinique, il a été observé que de 15 à 30 % des patients qui ont subi un infarctus du myocarde développent une dépression majeure. De plus, la population atteinte de dépression post-infarctus présente un risque de mortalité de trois à quatre fois plus élevé, et ce, en comparaison avec la population non dépressive post-infarctus. Dans un modèle de rat développé pour étudier la dépression post-infarctus, des cellules apoptotiques ont été retrouvées au niveau du système limbique. Il apparaît que les cytokines seraient en partie responsables de cette mort cellulaire qui relie le cœur en ischémie et le système nerveux central. Donc, les objectifs de cette thèse sont : 1) de caractériser spatialement et temporellement la survenue de la mort cellulaire par apoptose dans les structures du système limbique du rat, à la suite d’un infarctus du myocarde ; 2) de déterminer l’effet de l’anti-inflammatoire celecoxib sur cette apoptose observée au niveau de l’amygdale et de déterminer l’implication de l’enzyme COX-2 ; 3) de déterminer l’implication de la cytokine pro-inflammatoire TNF-α dans l’apoptose observée au niveau des structures du système limbique du rat, à la suite d’un infarctus du myocarde. Afin d’atteindre ces objectifs, les rats ont subi une ischémie de 40 minutes, suivi d’une période de reperfusion qui varie d’un protocole à l’autre (15 minutes, 24, 48, 72 heures ou 7 jours). De plus, en fonction du protocole, ces rats ont été traités avec soit du célécoxib (inhibiteur sélectif de la COX-2), soit avec du PEG sTNF-R1 (inhibiteur du TNF-α). À la suite de ces protocoles, les rats ont été sacrifiés, la taille de l’infarctus a été déterminée et les différentes structures cérébrales du système limbique prélevées. Des tests biochimiques propres à chaque protocole ont été réalisés afin de documenter l'apoptose. Il a alors été observé qu’aucun des deux traitements ne présentait d’effet sur la taille de l’infarctus. L’étude de l’apoptose dans le système limbique a révélé que : 1) le processus apoptotique se mettait en place dans l’hippocampe dès les 15 premières minutes de reperfusion suivant l’infarctus du myocarde et que ce processus était spatialement dynamique dans le système limbique jusqu’au septième jour postreperfusion ; 2) il est apparu que la COX-2 était impliquée dans l'apoptose du système limbique ; 3) il a été observé que le TNF-α périphérique était impliqué dans ce processus apoptotique après 72 heures de reperfusion en activant la voie extrinsèque de l'apoptose. Ces résultats ont permis de caractériser la survenue de l’apoptose au niveau du système limbique chez le rat à la suite d’un infarctus du myocarde et de documenter l'implication de la COX-2 et du TNF-α dans ce processus. Bien que ces résultats n’apportent pas de schémas thérapeutiques clairs ou de mécanismes physiopathologiques globaux ces derniers permettent une meilleure compréhension de la relation existante entre le cœur et le système nerveux central dans le cadre de l’infarctus du myocarde. De manière moins spécifique ils précisent la relation entre le système inflammatoire et le système nerveux central. / About 15 to 30% of clinical patients with myocardial infarction develop major depression. This population is three to four times more vulnerable to fatalities such as death when compared to the non depressed post-myocardial population. In a rat model, developed in order to study post myocardial infarct depression, apoptotic cells within the limbic system have been found. It has been shown that cytokines could be responsible for the cell death linking the ischemic heart to the central nervous system. Thus, the aims of this thesis are: 1) to characterize the spatial time course of the apoptotic cell death within the limbic system, following a myocardial infarct, in a rat model; 2) to determine the effect of the anti-inflammatory celecoxib on this apoptosis in the amygdala and determine the COX-2 enzyme’s implication; 3) to determine the implication of the pro-inflammatory cytokine TNF-α in the apoptosis observed within the limbic system, following a myocardial infarct, in a rat model. In order to achieve these goals, rats were submitted to 40 minutes of myocardial ischemia followed by a variable reperfusion period (15 minutes, 24, 48, 72 hours or 7 days). Moreover, depending on the protocol, rats were treated with celecoxib (COX-2 selective inhibitor), or with PEG sTNF-R1 (TNF-α inhibitor). At the end of each respective reperfusion period, rats were sacrificed, infarct size was determined and the different structures of the limbic system were dissected for further analysis. Biochemical tests, specific to each protocol were performed in order to characterize this apoptosis. With respect to obtained results, we observed that the infarct size was impacted by none of the two treatments. Apoptosis study within the limbic system revealed that: 1) the apoptotic process was activated in the hippocampus area within the first 15 minutes of reperfusion and this process was spatially dynamic in the limbic system until the seventh day of reperfusion; 2) it appeared that COX-2 was implicated in the apoptosis in the limbic system; 3) peripheral TNF-α was implicated in the apoptotic process after 72 hours of reperfusion by activating the extrinsic and intrinsic pathways of apoptosis. These results allowed characterization of apoptosis within the limbic system, in a rat model, following a myocardial infarct and the establishment of the implication of COX-2 and TNF-α in this process. Although these results do not provide any clear therapeutic schemas or global physiopathological mechanisms, they allow a better comprehension of the existing relationship between the heart and the central nervous system within the myocardial infarct context. To a less specific extent these results bring more information on the relationship between the inflammatory system and the central nervous system.

L'imagerie en tenseur de diffusion (DTI) permet de fournir un complément d'informations quantitatives au niveau tissulaire et sur le suivi des fibres de substance blanche. Elle nous a permis d'explorer chez des patients atteints d'épilepsie du lobe temporal (TLE) des anomalies cérébrales non détectables par les techniques d'imagerie conventionnelles. Dans ce travail de thèse nous avons combiné deux méthodes computationnelles s'appuyant l'une sur l'extraction d'informations dans des régions d'intérêts localisées et l'autre sur des mesures effectuées (moyennées) le long des fibres de substance blanche. L'identification de paramètres, à partir du tenseur de diffusion, a permis de mettre en évidence des modifications structurales de la substance blanche et de la substance grise, notamment au niveau des régions du système limbique (hippocampe, fornix, régions cingulaires, thalamus, amygdala). Trois groupes de sujets ont participé à cette étude : un groupe de patients atteints d'épilepsie du lobe temporal avec sclérose hippocampique (TLE+HS), un groupe de patients sans lésion visible sur l'IRM conventionnelle (TLE-HS) et un groupe de sujets volontaires. Les résultats obtenus ont montré des anomalies significatives dans les régions analysées chez les patients TLE-HS, différentes des celles retrouvées chez les patients TLE+HS. Les indices de tenseur de diffusion retenus ont permis de mettre en évidence une désorganisation structurale des régions du système limbique chez les patients TLE, spécialement dans le groupe sans lésion visible sur l'IRM conventionnelle / Diffusion tensor imaging (DTI) can provide quantitative information of brain abnormalities in patients with temporal lobe epilepsy (TLE). This technique allowed us to explore brain abnormalities that are not detectable with conventional magnetic resonance imaging (MRI).In this thesis we combined two computational methods: the first is based on information extraction from regions of interest and the second is based on measurements (averaged) along the white matter fibers. The identification of parameters from diffusion tensor has highlighted structural changes in the white matter and gray matter, particularly in the limbic system regions (hippocampus, fornix, cingulate regions, thalamus, amygdala). Three subject groups participated on this study: a patients group with temporal lobe epilepsy and a hippocampal sclerosis (TLE+HS), a patients group with TLE and normal conventional MRI (TLE-HS) and a healthy controls group. The results showed significant abnormalities in the analysed regions in patients with TLE-HS, different from those found in patients with TLE + HS. The selected diffusion tensor indices allowed us to highlight the structural disorganization of limbic system regions in patients with TLE, especially in patients with normal conventional MRI

Bc. Lucie Špuláková Signs of epilepsy spectrum disorder in drug-dependent persons Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Specialist in laboratory methods Objectives: The objective of this diploma thesis was to demonstrate the signs of epile- psy spectrum disorder in risk group of drug-dependent persons. Methods: We investigated the signs of epilepsy spectrum disorder by questionnaire survey - specifically by questionnaires Limbic System Checklist-33 (LSCL-33) and Complex Partial Seizure-like Symptoms Inventory (CPSI). We used statistical methods for results evaluation - the percentage comparison, chi-square test, and Spearman corre- lation coefficient. Results: The questionnaire survey demonstrated a significant shift towards abnormal values for both questionnaires. Abnormal score was achieved by 77 % respondents for questionnary LSCL-33, suspected score was achieved by 19 % respondents. Score for epilepsy spektrum disorder was achieved by 32 % respondents for questionnary CPSI and 45 % respondents showed unusual values. Conclusions: Signs of epilepsy spectrum disorder in drug-dependent persons was thus proved. The incidence is higher than in ordinary population and population of smokers. It was also...

Os estudos dos processos cognitivos propiciam um cenário promissor para a realização de pesquisas visando uma maior compreensão de como o funcionamento do cérebro pode favorecer a educação, possibilitando o desenvolvimento de novas teorias e abordagens que estimulem a aprendizagem. O presente trabalho abordará principalmente como se dá a aquisição, o armazenamento, processamento e a recuperação do conhecimento do ponto de vista da neurociência e de que forma o mapa conceitual (MC) pode mapear o conhecimento do indivíduo. O MC pode ser utilizado tanto como uma estratégia de aprendizagem para a compreensão de conceitos-chave bem como as relações entre estes quanto para promover o pensamento crítico do indivíduo. É uma representação gráfica bidimensional cuja estrutura permite organizar visualmente as relações entre conceitos que podem ser indicadas por palavras, frases e símbolos. É usado para facilitar o aprendizado ao hierarquizar os conceitos por meio de construções significativas para o indivíduo. Os conceitos aparecem nas caixas e as relações nas linhas que os unem: a dois conceitos conectados chamamos de proposição. Durante a construção de um MC o indivíduo exercita a sua capacidade de estabelecer relações entre o conhecimento que já tem e o adquirido no decorrer da aprendizagem ao representar graficamente os conceitos sobre um determinado assunto. / The study of cognitive processes provide a promising scenario to research aimed at better understanding of how the functioning of the brain may promote the education, enabling the development of new theories and approaches that encourage learning. This work will mainly occurs as the acquisition, storage, processing and retrieval of knowledge from the viewpoint of neuroscience, and how the conceptual map can map the knowledge of the individual. The conceptual map (CM) can be used both as a strategy of learning for the understanding of key concepts and relations between them and to promote critical thinking of the individual. Two-dimensional graphical representation, the CM allows visually organize the relationships between concepts. This structure from the wider concepts up to less comprehensive and relations between them can be indicated by words, phrases and symbols. It is used to facilitate the learning concepts ranking by building significant to the individual. The concepts appear in the boxes and lines that unite them: two concepts connected call proposition. During the construction of a CM, the individual exercises its ability to establish relationships between knowledge that he has already acquired in the course of learning to represent graphically the concepts of a particular subject.

Les encéphalites limbiques à autoanticorps anti-CASPR2 sont des atteintes du système nerveux central caractérisées par des troubles de la mémoire et des crises d’épilepsie. La protéine CASPR2 (Contactin-associated protein-like 2), avec son partenaire TAG-1, est connue pour son rôle dans le rassemblement des canaux potassiques voltage-dépendants (Kv1.1 et Kv1.2) dans la région juxtaparanodale des nœuds de Ranvier ; régions essentielles pour la conduction rapide des messages nerveux. Par ailleurs, de plus en plus d’études suggèrent un rôle de CASPR2 dans la plasticité synaptique et l’excitabilité neuronale, en lien avec les symptômes observés chez les patients présentant des anticorps anti-CASPR2. Cependant, le rôle pathogénique des anticorps anti-CASPR2 dans les encéphalites limbiques reste loin d’être compris. Au cours de ma thèse, j’ai souhaité améliorer la connaissance des mécanismes pathologiques des anticorps anti-CASPR2 de patient dans l’encéphalite limbique auto-immune. Pour cela, j’ai déterminé les caractéristiques biologiques des anticorps anti-CASPR2, suggérant un rôle direct des anticorps sur la fonction de CASPR2 en ciblant les domaines N-terminaux de la protéine. De plus, j’ai identifié deux mécanismes d’action potentiels des anticorps anti-CASPR2 sur l’interaction entre CASPR2 et TAG-1 et sur l’expression des canaux Kv1.2 en surface. Ces travaux impliquent d’avantage les anticorps anti-CASPR2 dans la pathogénicité des encéphalites limbiques auto-immunes / Anti-CASPR2 autoimmune limbic encephalitis is a central nervous system disorder characterized by memory disorders and epilepsy. CASPR2 (Contactin-associated protein-like 2) with its partner TAG-1, is known for its role in the clusterisation of voltage-dependent potassium channels (Kv1.1 and Kv1.2) in the juxtaparanodal region of node of Ranvier; which are essential for the rapid conduction of nerve signals. In addition, an increasing number of studies suggest a role of CASPR2 in synaptic plasticity and neuronal excitability, in relation with the symptoms observed in patients with anti-CASPR2 antibodies. However, the pathogenic role of anti-CASPR2 antibodies in limbic encephalitis remains far from clear. During my thesis I wished to improve our understanding of the mechanisms mediated by anti-CASPR2 antibodies in limbic encephalitis. To this end, I determined the biological characteristics of anti-CASPR2 antibodies, suggesting a direct role of antibodies on CASPR2 function by targeting its N-terminal domains. Furthermore, I identified two potential mechanisms of anti-CASPR2 antibodies on CASPR2/TAG-1 interaction and on Kv1.2 cell surface expression. These works further implicate anti-CASPR2 antibodies in the pathogenicity of autoimmune limbic encephalitis

INTRODUÇÃO: O processamento emocional pelo cérebro humano tem sido atualmente investigado através do uso de ressônancia magnética funcional (RMf). A RMf possibilita o estudo in vivo e não invasivo de mudanças na atividade cerebral regional em voluntários humanos saudáveis. O processamento emocional pode ser modulado através do uso de antidepressivos que influenciam sistemas neurais relacionados ao processamento emocional, através da modulação da ação de neurotransmissores como a serotonina e a noradrenalina. A clomipramina, um antidepressivo tricíclico, tem sido relacionada com efeitos de resposta clínica mesmo em voluntários saudáveis. Estudos utilizando a RMf permitem a investigação do efeito de antidepressivos nos sistemas neurais envolvidos no processamento emocional em indivíduos saudáveis que apresentam resposta ao uso destes medicamentos comparados a sujeitos que não apresentam resposta ao tratamento. MÉTODOS: Nesta tese, dezoito voluntários saudáveis foram investigados em relação a mudanças de atividade neural em resposta à indução emocional através da apresentação de fotografias do International Affective Pictures System (IAPS). Foram estudadas particularmente as emoções de raiva, felicidade e medo. Os voluntários foram submetidos ao tratamento prolongado com doses baixas de clomipramina por quatro semanas. A amostra foi subdividida em respondedores (n=6) e não respondedores (n=12) ao tratamento com clomipramina. A atividade neural foi estimada com o uso da RMf, através da mensuração do efeito blood oxygenation level dependent (BOLD). As imagens foram processadas e analisadas usando o programa Statistical Parametric Mapping (SPM). Indivíduos não respondedores foram comparados sob o efeito e na ausência de efeito da clomipramina, através de comparações planejadas utilizando t-teste pareado. Indivíduos respondedores foram comparados com os não respondedores sob o efeito da clomipramina através de t-teste não pareado. RESULTADOS: Nos voluntários não respondedores à clomipramina, a comparação entre os estados medicado versus não medicado evidenciou menor atividade neural na região da amídala quando sob efeito da clomipramina em resposta a estímulos de valência negativa. Demonstramos ainda, em paradigmas de valência positiva e negativa, diminuição da atividade neural no giro do cíngulo anterior, na ínsula e no putâmen na vigência da medicação. Quando foram comparados os indivíduos respondedores com os não respondedores sob efeito de clomipramina, um aumento consistente de atividade cerebral foi observado nos voluntários respondedores na região da ínsula. CONCLUSÕES: O uso prolongado de doses baixas de clomipramina apresentou ação em regiões cerebrais envolvidas com o processamento emocional. Quando indivíduos não respondedores foram comparados sob o efeito e sem o efeito da clomipramina, foi observada menor atividade amidalar durante o tratamento em resposta a estímulos de valência negativa, possivelmente devido à menor demanda neural na avaliação inicial do estímulo de valência negativa. Também foi observada menor ativação no giro do cingulo anterior, na ínsula e no putâmen na vigência do uso da clomipramina, possivelmente em associação a uma diminuição do mapeamento cortical de funções interoceptivas em resposta a estímulos emocionais positivos e negativos. Quando indivíduos respondedores foram comparados com os não respondedores ao tratamento prolongado com doses baixas de clomipramina, foi observada maior ativação insular nos indivíduos respondedores quando estavam sob efeito de clomipramina; estes resultados indicam que possivelmente os indivíduos que respondem ao tratamento antidepressivo são os que percebem mais as alterações de seu estado corporal durante o processamento emocional. / INTRODUCTION: The emotional processing by the human brain has now been investigated through the use of functional magnetic resonance imaging (fMRI). The fMRI technique allows the noninvasive study of in vivo changes in regional brain activity in healthy human volunteers. The emotional processing may be modulated through the use of antidepressants that influence neural systems linked to emotional processing, by modulating the action of neurotransmitters such as serotonin and norepinephrine. Clomipramine, a tricyclic antidepressant, has been reported to elicit clinical response even in healthy volunteers. Studies using fMRI allow the investigation of the effect of antidepressants on neural systems involved in emotional processing in healthy subjects showing response to the use of antidepressant drugs compared to subjects who do not respond to treatment. METHODS: In this thesis, eighteen healthy volunteers were investigated in relation to changes in neural activity in response to emotional induction through the presentation of photos of the International Affective Picture System (IAPS). We studied especially the emotions of anger, happiness and fear. The volunteers were subjected to prolonged treatment with low doses of clomipramine for four weeks. The sample was divided into responders (n = 6) and non-responders (n = 12) to treatment with clomipramine. The neural activity was estimated by using fMRI, by measuring the blood oxygenation level dependent effect (BOLD). Images were processed and analyzed using the Statistical Parametric Mapping (SPM) program. Non-responders were compared under two conditions: when using clomipramine, and after drug washout, using paired t-tests. Individuals who responded to clomipramine treatment were compared with non-responders under the effect of the drug by independent t-test. RESULTS: In volunteers not responding to clomipramine, a comparison between the non-medicated versus medicated states showed less neural activity in the region of the amygdala when under effect of clomipramine in response to stimuli of negative valence. We also demonstrated, both in the paradigms of positive and negative valence, decreased neural activity in the anterior cingulate gyrus, insula and putamen during the medicated state. When responders were compared with non-responders under the effect of clomipramine, a consistent increase in brain activity was observed in the former group in the insula. CONCLUSIONS: The prolonged use of low doses of clomipramine induced activity changes in brain regions involved in emotional processing. When non-responders were compared under the influence and without the effect of clomipramine, the amygdala displayed lower activity during treatment in response to stimuli of negative valence, possibly due to lower demand in the initial evaluation of stimuli of negative valence. There was less activation in the anterior cingulate gyrus, insula and putamen during the use of clomipramine, possibly in association with a decrease in the cortical mapping of interoceptive changes in response to positive and negative emotional stimuli. When responders were compared with non-responders after prolonged treatment with low doses of clomipramine, insular activation was greater in responders when individuals were under the effect of clomipramine. These results indicate that individuals who respond to antidepressant treatment are those who perceive more changes in their bodily state during emotional processing.

Ce travail s'inscrit dans l'étude du réseau neuronal responsable de l'activation corticale au cours du sommeil paradoxal (SP) chez le rongeur. Dans la première partie de ma thèse, j'ai participé à la démonstration que cette activation est limitée à quelques structures limbiques déterminantes pour l'apprentissage, dont le gyrus dentelé de l'hippocampe (GD). Nous avons ensuite montré que l'activation du GD en SP est due à une projection issue du noyau supramammillaire (Sum). J'ai ensuite montré en combinant l'hybridation in situ d'un marqueur des neurones glutamatergiques et GABAergiques et l'immunohistochimie du FOS que les neurones du Sum latéral actifs en SP sont à la fois glutamatergiques et GABAergiques (GLU/GABA). Enfin, j'ai montré que l'augmentation du nombre de neurones FOS+ dans le GD dorsal en SP est abolie après la lésion neurochimique du Sum. De plus, la lésion du Sum induit une nette réduction de la densité de fibres glutamatergiques dans le GD dorsal. Ces résultats indiquent que les neurones du GD dorsal sont activés en SP par les neurones GLU/GABA du Sum latéral. Le deuxième objectif de ma thèse a été de déterminer la fonction de cette voie en SP. Ainsi j'ai utilisé la technique d'optogénétique afin d'inactiver ou activer les fibres GLU/GABA provenant du Sum localisées dans le GD dorsal au cours du SP. Nos résultats montrent que l'activation de ces fibres en SP induit une augmentation de la fréquence et de la puissance du thêta enregistré dans le GD. Ces résultats indiquent que la voie Sum-GD dorsal contrôle le thêta hippocampique et soutiennent l'hypothèse d'un rôle de cette voie dans les processus de consolidation mnésique prenant place au cours du SP / During my PhD I studied the neuronal network responsible for cortical activation during paradoxical sleep (PS) in rodents. In the first part of my thesis, I participated to the demonstration that this activation is limited to a few limbic structures involved in learning, including the dentate gyrus of the hippocampus (DG). Then, we showed that the activation of DG during PS is due to a projection from the supramammillary nucleus (Sum). Besides, by combining the in situ hybridization of markers of GABAergic and glutamatergic neurons and FOS immunohistochemistry, I demonstrated that lateral Sum neurons active in SP are both glutamatergic and GABAergic (GLU/GABA). Finally, I showed that the increasing number of FOS+ neurons in the dorsal DG during PS is abolished by the neurochemical lesion of the Sum. In addition, the Sum lesion induces a clear reduction of the density of glutamatergic fibers in the dorsal DG. These results indicate that during PS, dorsal DG neurons are activated by GLU/GABA neurons located in the lateral Sum. The second aim of my thesis was to determine the function of this pathway during PS. To realize that, I inactivated or activated by optogenetics the Sum GLU/GABA fibers located in the dorsal GD during SP. Our results show that the activation of these fibers during SP induces an increase in the theta frequency and power recorded in the dorsal DG. These results indicate that the Sum-dorsal DG-pathway modulates the hippocampal theta and supports the hypothesis of a role of this pathway in the memory consolidation process during SP