Existem evidências de que dietas compostas por níveis elevados de lipídeos e/ou car-boidratos contribuem para o desenvolvimento de doenças crônico-degenerativas e de déficit cognitivo. Entretanto, os mecanismos pelos quais a obesidade materna interfere na saúde da prole, especificamente no metabolismo e na memória de longo-prazo, ain-da são pouco claros. O objetivo deste trabalho foi investigar se a obesidade materna interfere no metabolismo e nos comportamentos relacionados à memória de longo-prazo de seus filhotes, e se há um efeito somatório com a exposição à dieta de cafete-ria no decorrer da vida da prole. Ratas foram alimentadas com dieta controle (CON) ou de cafeteria (CAF) desde o desmame até os 210 dias de vida, no desmame de sua pro-le. A partir do desmame, seus filhotes machos foram divididos em 4 grupos (CON-CON, CON-CAF, CAF-CON e CAF-CAF) para que todas as ninhadas ingerissem CON ou CAF, independentemente da dieta materna. As mães foram decapitadas no dia seguin-te ao desmame dos filhotes. Foi decapitada e analisada em tarefas comportamentais metade dos filhotes aos 30 dias de idade e, a outra metade, aos 120 dias. As mães CAF apresentaram maior peso corporal total e de tecido adiposo e maiores concentra-ções circulantes de colesterol total, insulina e leptina do que as mães CON. A ingestão calórica semanal dos filhotes que ingeriram CAF mostrou-se maior do que os que inge-riram CON, independentemente da dieta materna. As ninhadas apresentaram peso cor-poral igual no desmame e aos 30dias, porém aos 120dias, os filhotes que ingeriram CON-CAF tiveram aumento de peso em relação aos filhotes CON, independentemente da dieta materna destes. Porém, os filhotes CAF-CAF tiveram redução do peso corporal em relação aos CON-CAF na idade adulta. Aos 30 e 120 dias, os filhotes que ingeriram CAF apresentaram peso de tecido adiposo maior do que os que ingeriram CON, inde-pendentemente da dieta materna. Aos 30 e 120dias, a trigliceridemia e a colesterolemia estavam iguais entre os grupos, assim como a glicemia aos 30 dias. Porém, aos 120 dias, os filhotes que ingeriram CAF apresentaram hiperglicemia, assim como hiperlepti-nemia e hiperinsulinemia, independentemente da dieta materna. Aos 30 dias, todos os grupos que foram expostos à dieta de cafeteria em alguma etapa da vida apresentaram declínio no desempenho em uma ou nas duas tarefas relacionadas à memória de lon-go-prazo (Reconhecimento de objetos e Esquiva Inibitória step-down). Já aos 120 dias, o grupo CAF-CAF foi o único que mostrou piora no desempenho na tarefa de Reconhe-cimento de Objetos, e todos os grupos mostraram capacidade de aprendizado e memó-ria na tarefa de Esquiva Inibitória step-down. Esses dados sugerem que a dieta materna modula o peso corporal e comportamentos relacionados à memória de longo-prazo dos filhotes e que seus efeitos sofrem influência da dieta pós-natal da prole. Porém, novos estudos são necessários para elucidar os mecanismos envolvidos no desenvolvimento dessas alterações. / There is evidence that diets containing high levels of lipids and / or carbohydrates con-tribute to the development of chronic degenerative diseases and cognitive impairment. However, the mechanisms by which maternal obesity affects health of offspring, specifi-cally in metabolism and long-term memory, are still unclear. The aim of this study was to investigate whether maternal obesity interferes with the metabolism and behavior related to long-term memory of their offspring, and if there is a summation effect with exposure to the cafeteria diet during the life of the offspring. Rats were fed a control diet (CON) or cafeteria (CAF) from weaning to 210 days old at weaning of their offspring. After wean-ing, their male offspring were divided into 4 groups (CON-CON, CON-CAF, CAF and CAF-CON-CAF) for all litters ingest CON or CAF, irrespective of maternal diet. Mothers were decapitated on the day following weaning of pups. Was decapitated and analyzed in behavioral tasks half the pups at 30 days of age and the other half at 120 days. CAF mothers had higher total body weight and adipose tissue and increased circulating con-centrations of total cholesterol, insulin and leptin than mothers CON. The weekly caloric intake of pups that ingested CAF was higher than those who ate CON, regardless of maternal diet. Litters showed body weight equal to weaning and 30days, but the 120dias, puppies who ate CON-CAF had weight gain compared to CON offspring, re-gardless of maternal diet these. However, the pups CAF-CAF had reduced body weight compared to CON-CAF adulthood. At 30 and 120 days, the puppies that ingested CAF showed greater weight of adipose tissue than those who ate CON, irrespective of ma-ternal diet. At 30 and 120dias, blood triglyceride and cholesterol were similar between groups, as well as blood glucose levels at 30 days. However, at 120 days, the puppies that ingested CAF showed hyperglycemia, as hiperlepti-nemia and hyperinsulinemia, irrespective of maternal diet. At 30 days, all groups were exposed to the cafeteria diet at some stage of life show a decline in performance in one or both tasks related to long-term memory (Recognition of objects and Dodge inhibitory step-down). Already at 120 days, the group CAF-CAF was the one who showed deterioration in performance in the task of Object Recognition, and all groups showed learning ability and memory in the inhibitory avoidance task step down. These data suggest that maternal diet modulates body weight and behaviors related to long-term memory of the puppies and their effects are influenced by postnatal diet offspring. However, further studies are needed to eluci-date the mechanisms involved in the development of these changes.

Les expériences qui jalonnent la vie favorisent la survenue de modifications cérébrales durables et pouvant impacter les fonctions cognitives, ainsi que le développement de troubles cérébraux. L'hippocampe est une structure cérébrale qui joue un rôle essentiel dans l'apprentissage et la mémoire. Dans la première étude, nous avons montré comment l'activité neuronale sous-tendant les processus de la mémoire influence fortement l'intégration des nouveaux neurones hippocampiques dans le cerveau adulte, suggérant une modulation durable de la fonction hippocampique. Dans la deuxième étude, nous avons montré que le séjour en milieu enrichi qui prévient les déficits mnésiques liés à l'âge et induit également des modifications épigénétiques dans le cerveau sain et modèle de la maladie d'Alzheimer. Ceci suggére que des règulations épigénétiques durables pourraient soutenir les effets promnésiques de l'enrichissement environnemental. Ainsi, cette thèse a mis en évidence dans l'hippocampe, l'existence de plasticité dépendante de l'activité dans le cerveau sain et modèle de la maladie d'Alzheimer. Cette plasticité pourrait être une cible pertinente dans le traitement de certaines conditions pathologiques. / Throughout life, environmental challenges promote long-lasting changes within the brain that can affect cognitive function, as well as the development of brain disorders. Within the brain, the hippocampus plays a key role in learning and memory processes. In the first study, we demonstrate how neuronal activity triggered by the learning and memory enhances the synaptic integration of adult-born hippocampal neurons that could support hippocampal function. In the second study, we show that enriched environment prevents age-related memory deficits and induces epigenetic modifications in both healthy and Alzheimer's disease conditions. This suggests that long-lasting epigenetic regulations may participate in sustaining the promnesic effects of environmental enrichment. Altogether, this thesis provides evidence of activity-dependent plasticity in the hippocampus in healthy and diseased brain, and suggests that stimulating such plasticity may contribute to improve pathological conditions.

Le cortex préfrontal médian (mPFC) est nécessaire pour la formation desreprésentations contextuelles et l’expression de la mémoire suite au conditionnementde peur. Des études récentes ont montré des changements dépendants del’apprentissage dans l’excitabilité intrinsèque des neurones du mPFC. Il n’estcependant pas établit, si ces changements se font à l’échelle régionale ou s’ils sontspécifiques du type neuronal. La connectivité spécifique et les propriétés intrinsèquesde différents types neuronaux pourraient entrainer certaines populations neuronales àêtre préférentiellement impliquées dans le traitement de l’information au cours d’unetâche d’apprentissage. Dans ce projet, nous avons étudié cette hypothèse par l’étudede la plasticité de l’excitabilité intrinsèque dans la partie prélimbique (PL) du mPFCdans deux groupes neuronaux bien définis : ceux projetant vers l’amygdaleipsilatérale et ceux projetant vers le mPFC controlatéral. Nous avons utilisé à la fois leconditionnement à la peur contextuelle, un traçage rétrograde, et des enregistrementsélectrophysiologiques en cellule entière des neurones pyramidaux marqués chez lessouris mâles C57bl/6J adultes âgées de 2 à 3 mois. Nous montrons que l’excitabilitédes neurones projetant vers l’amygdale présentent des changements dépendants del’apprentissage, suite au conditionnement de peur contextuelle. En revanche,l’excitabilité des neurones projetant vers le mPFC controlatéral ne présente pas dedifférence entre les animaux entrainés et témoins. Ensemble, ces résultats indiquentque les changements induits par l’apprentissage dans l’excitabilité intrinsèque ne sontpas généralisés à tous les neurones du PL mais sont par contre définis par les ciblesdes neurones qui projettent sur de longues distances. / The medial prefrontal cortex (mPFC) is necessary for the formation of contextualrepresentations and memory expression following fear conditioning. Recent studieshave shown learning-dependent changes in the intrinsic excitability of mPFC neurons.It is not clear, however, whether these changes are region-wide or neuron-typespecific. The specific connectivity and intrinsic properties of different neuronal typescould cause certain neuronal populations to be preferentially involved in informationprocessing in a learning paradigm. In this project, we investigated this hypothesis bystudying the plasticity of intrinsic excitability in the prelimbic (PL) part of the mPFCin two defined neuronal groups: those projecting to the ipsilateral amygdala and thoseprojecting to the contralateral mPFC. We used contextual fear conditioning togetherwith retrograde tracing and whole-cell electrophysiological recordings of labelledpyramidal neurons in adult 2-3 month old male C56BL/6J mice. We show thatneurons projecting to the amygdala display learning-dependent changes in neuronalexcitability following contextual fear conditioning. In contrast, the excitability ofneurons projecting to the contralateral mPFC does not differ between trained andcontrol animals. Together, these results indicate that learning-induced changes inintrinsic excitability are not generalised across all PL neurons but instead are definedby the neurons’ long-range projection targets.

In this work, we examined the executive functions of the hippocampus at the behavioral level as a so-called behavioral separation in adult rats. We studied an impact of day-to-day alternation versus sequential learning (and the order of learning) of two spatial tasks (Morris Water Maze and Active Allothetic Place Avoidance) testing different hippocampal functions (experiment 1), or an impact of sequential versus alternating learning of one task (Active Allothetic Place Avoidance) in two different rooms (experiment 2), on performance. We found out that rats are able to learn both tasks as well as to discriminate between the two contexts regardless of the order or alternating of learning. Because such executive functions are impaired in human patients suffering from schizophrenia, we used this procedure also in the rat model of schizophrenia induced by acute intraperitoneal application of dizocilpine (MK-801), glutamate NMDA receptors antagonist, in the dose of 0.08 mg/kg. We failed to selectively disrupt the behavioral separation, however, we observed general learning deficit and hyperlocomotion regardless of the alternation in the Active Allothetic Place Avoidance task in these rats. The cognitive impairments in connection with learning after such low dose of MK-801 in this task have not yet been...

Due to the persisting lack of reliable animal models of cognitive impairment with good translational validity, researches strive to discover new ways and tools to replicate symptoms of human neurodegenerative diseases in rodents. Recently, biperiden, an M1- selective muscarinic antagonist, has been proposed as a potential tool for generating fast screening models of mnemonic deficits such as seen in patients with Alzheimer's disease. Being highly selective for the M1 receptor, a predominant type of muscarinic acetylcholine receptors in the brain involved in cognitive processes, it has been speculated to possibly only influence cognition without causing sensorimotor side effects. Studies assessing the usability of this drug reported conflicting results. We have decided to expand the experimental data and evaluate biperiden's validity in several variants of the Morris water maze. The results of this study showed no significant effect of biperiden on cognitive flexibility, tested by reversal learning. In delayed-matching-to-position paradigm, which tests assesses working memory, we found a difference in performance between the two experimental groups; however, it cannot be unequivocally attributed to a memory impairment. No effects were observed in visible platform task, confirming a lack of...

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本實驗室於先前利用莫氏水迷津試驗篩選學習快與學習慢的大白鼠，取出其海馬迴組織並進行聚合酶連鎖反應差異顯示(PCR differential display)，結果顯示學習快與學習慢的大白鼠背側海馬迴之間共有98個cDNA片段有差異表現。把這些cDNA片段進行定序並利用BLAST資料庫比對，其中一個cDNA片段為大白鼠的pias1 [protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1)] 基因。為了瞭解pias1基因的表現是否和空間學習有所關聯，隨機把大白鼠分成兩組，一組為有訓練組別(有空間線索與隱藏式平台)，另一組為無訓練的組別(沒有平台，作為游泳的控制組)同時進行莫氏水迷津學習試驗。試驗完畢，取出海馬迴組織進行即時定量聚合酶連鎖反應與西方墨點法來分析PIAS1的mRNA與蛋白質的表現。結果顯示有水迷津訓練的大白鼠，其PIAS1的mRNA與蛋白質表現皆明顯的高於無訓練的組別。為了更進一步確認PIAS1在空間學習中所扮演的角色，我們利用基因轉染的技術，轉染PIAS1 siRNA至大白鼠海馬迴CA1區域抑制PIAS1的表現。我們發現轉染PIAS1 siRNA至CA1區域會抑制大白鼠在水迷津的行為表現，然而轉染野生型的PIAS1質體基因至CA1區域卻會增進水迷津試驗的學習能力，同時我們也以西方墨點法發現，當轉染PIAS1 siRNA會增加STAT1 Tyr701的磷酸化，而轉染PIAS1 WT則會抑制STAT1 Tyr701的磷酸化。為了探討PIAS1促進記憶形成的分子機制，我們發現當轉染突變型的STAT1 Y701F質體基因至CA1區域，會抑制PIAS1 siRNA所造成記憶的損害。這些實驗結果代表著PIAS1會抑制STAT1 Tyr701的磷酸化，而PIAS1促進記憶的形成可能是藉由抑制STAT1 Tyr701的磷酸化而達成。另外，我們也單獨轉染突變型的STAT1 Y701F質體基因至CA1區域，水迷津實驗結果顯示會促進空間記憶的形成。目前PIAS1在免疫的角色已有許多研究證實，但是本篇研究是第一個提出PIAS1會參與哺乳類動物學習與記憶形成探討。 / Our laboratory has previously identified 98 cDNA fragments by using PCR differential display from rat dorsal hippocampus that are differentially expressed between fast learners and slow learners from the water maze learning task. After sequencing and BLAST analysis, one of these cDNA fragments encodes the rat pias1 [protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1)] gene. In order to determine whether pias1 gene expression is associated with spatial learning, naïve rats were randomly assigned to the trained group (with visual cues and platform been present) and the non-trained group (without the platform as the swimming control). The dorsal hippocampus from these animals was dissected out at the end of the training and was subjected to RNA and protein extraction for real-time PCR and Western blot analysis of PIAS1 expression, respectively. Results revealed that the pias1 mRNA level and protein level was both higher in the hippocampus of trained rats than non-trained rats. To further examine the role of PIAS1 involved in spatial learning and memory, the specific PIAS1 siRNA was used to knockdown the expression of PIAS1 in rat hippocampal CA1 region. We found that transfection of PIAS1 siRNA to the CA1 area impaired water maze performance, whereas transfection of the wild-type PIAS1 DNA plasmid to the CA1 area facilitated water maze performance in rats. Meanwhile, PIAS1 siRNA increased STAT1 phosphorylation at Tyr701 whereas PIAS1 WT decreased STAT1 phosphorylation at this residue. In the examination of molecular mechanism underlying PIAS1-mediated memory facilitation, we have found that transfection of the STAT1 Y701F mutant plasmid antagonized the memory-impairing effect of PIAS1 siRNA, whereas transfection of STAT1 Y701F alone facilitated spatial memory formation. These results together suggest that one of the molecular mechanisms underlying PIAS1-mediated memory facilitation is through decreased STAT1 phosphorylation at Tyr701. All these manipulations did not affect visible platform learning in rats. In addition to the well documented role of PIAS1 in the immune system, here we have been the first to demonstrate a novel role of PIAS1 involved in spatial memory formation in rats.

Das Gesangssystem der Vögel hat sich als ein hervorragendes Modellsystem erwiesen, um Fragen zu Mechanismen entwicklungsbedingter neuronaler Plastizität von Lernprozessen zu erarbeiten. Bei Singvögeln haben sich im Laufe der Phylogenese neuronale Zentren entwickelt, die sich auf das Gesangslernen und die Gesangsproduktion spezialisiert haben. Zebrafinkenmännchen, wie viele andere Singvögel auch, erlernen ihren Gesang, indem sie von einem Tutor ihr artspezifisches Gesangsmuster schon in früher Jugend im Gedächtnis abspeichern und dann ganz allmählich ihr eigenes Vokalisationsmuster über auditorische Rückkopplung an das im Gehirn abgespeicherte Muster angleichen. Parallel zu diesen Verhaltensänderungen, finden auch auf neuronaler Ebene zahlreiche Veränderungen in den Gesangskernen statt, die in der hier vorliegenden Arbeit detailliert untersucht wurden, indem Zebrafinken zum einen mit einem Gesangstutor aufwuchsen oder ohne ein Gesangsvorbild. Die Folgen dieser unterschiedlichen Aufzuchtsbedingungen wurden dann im Gesang und in den neuronalen Strukturen der Gesangskerne mit einer Vielzahl von Techniken analysiert, einschließlich der Golgi-Technik, Elektronenmikroskopie, Immunhistochemie, verschiedener neuronaler Tracersubstanzen und quantitativer Stereologie, sowie intrazellulärer Ableitungen am in vitro Hirnschnittpräparat. Die Daten zeigen u.a., dass dendritische Spines an der Gedächtnisbildung für Gesang maßgeblich beteiligt sind und zwar in einer Vorderhirnregion, der eine wichtige Rolle bei frühen sensorischen Lernprozessen zukommt, dem lateralen magnocellularen Nucleus des anterioren Nidopalliums (LMAN). Zebrafinkenweibchen singen nicht und haben weitaus kleinere Gesangskerne als die Männchen. Zebrafinkenweibchen, die nie einen artspezifischen Gesang hören, weisen im Vergleich zu denen, die mit einem solchen aufgewachsen sind, signifikante Unterschiede in der neuronalen Struktur im Nucleus robustus arcopallii (RA) auf. Diese Befunde zeigen, dass die Gesangskerne bei Weibchen trotz ihrer kleineren Größe dennoch eine wichtige Rolle bei der Gedächtnisbildung eines artspezifischen Gesangsmusters spielen. Man beachte, dass die Nomenklatur des Vogelgehirns 2004 revidiert wurde (Reiner et al, J Comp Neurol 473:377-414, 2004; http://avianbrain.org/papers/RevisedNomenclature.pdf). / The song system of birds has been used extensively as a model system for studying basic mechanisms of neuronal plasticity and development underlying a learned behavior. Discrete sets of interconnected nuclei in the avian brain have evolved and are a prerequisite for song learning processes and the production of song. Zebra finch males, like many other song birds, learn their song by memorizing a tutor song model early in life and then gradually matching their vocal output by auditory feedback to the stored memory of that tutor song. In parallel to these behavioural changes, various changes in neuronal structures of song system nuclei take place. These structural correlates of song learning processes have been investigated in great detail in the current research by raising zebra finches with and without a song tutor model and then studying the consequences for song and for neuronal structure in the song system by using a variety of techniques including Golgi-technique, electron microscopy, immunohistochemistry, various neuronal tracer and quantitative stereology, intracellular recordings in the in vitro slice preparation and analyzing sonograms at the behavioral approach. There is strong evidence that, among other findings, dendritic spines are very much involved in memory formation of song in the lateral magnocellular nucleus of the anterior nidopallium (LMAN), a forebrain region particularly involved in sensory learning processes early in life. Female zebra finches do not sing and have much smaller song nuclei than males. Rearing females either with being exposed to species-specific song early in life or deprived of hearing song, exhibit significant differences in neuronal structure particularly in nucleus robustus arcopallii (RA). These data give further evidence that, despite their smaller sizes, song system nuclei in female birds do play an important role in memorization of song. Please note that in 2004 the nomenclature of the avian brain has been revised (Reiner et al, J Comp Neurol 473:377-414, 2004; http://avianbrain.org/papers/RevisedNomenclature.pdf).

Im Subikulum der Ratte finden sich zwei unterschiedliche Typen von Pyramidalzellen, die sich auf Grund ihres intrinsischen Entladungsverhaltens unterscheiden. Die Funktion dieser beiden Zelltypen hinsichtlich der synaptischer Neurotransmission ist unklar. Bursterzellen und regulär feuernde Zellen zeigten nach tetanischer Reizung ein unterschiedliches Ausmaß der LTP. Neben der zellspezifischen Ausprägung der LTP fanden sich mehrere Hinweise auf eine zielspezifische Projektion der Efferenzen der vorgeschalteten Area CA1. Die durchgeführten Experimente legen den Schluss nahe, dass Axone von Pyramidalzellen der Area CA1 selektiv auf subikuläre Pyramidenzellen projizieren und so den hippokampalen Informationsfluss steuern und regulieren können. NMDA-Rezeptoren auf beiden Seiten des synaptischen Spaltes spielen hier eine besondere Rolle. Präsynaptische NMDAR der Untereinheit NR2B scheinen an der LTP in Bursterzellen beteiligt zu sein und über einen vermehrten Kalziumeinstrom in die Präsynapse eine langanhaltende Erhöhung der Transmitterausschüttung herbeizuführen. Ebenso zeigten sich abhängig von der Zielzelle Hinweise auf eine unterschiedliche Aktivierung der präsynaptischen Adenylylcyclase-cAMP Kaskade. In Pilokarpin-behandelten Tieren ließ sich nach hochfrequenter Reizung keine langanhaltende Potenzierung der synaptischen Antworten nachweisen. Stattdessen scheinen polysynaptisch latente Verbindungen mittels tetanischer Stimulation aktivierbar zu sein. In einigen Fällen waren diese polysynaptisch latenten Verbindungen per se, in anderen Fällen nach Blockade der GABAergen Neurotransmission aktiv. In Hirnschnittpräparaten von Patienten mit pharmakoresistenter Temporallappenepilepsie konnte im Subikulum spontane rhythmische Aktivität mit einer Frequenz von 0,75 bis 3 Hz aufgezeichnet werden. Diese Aktivität, bestehend aus EPSP/IPSP Sequenzen, wurde sowohl in sklerotischem als auch in nicht sklerotischem Gewebe gefunden. In beiden Gruppen korrelierte die in vitro Aktivität sehr gut mit dem präoperativen Auftreten elektroenzephalografisch detektierter interiktaler Aktivität. Die Blockade GABAerger oder glutamaterger Neurotransmission hob die inhibitorische bzw. exzitatorische Aktivität auf. Dies legt den Schluss nahe, dass sowohl Interneurone wie Pyramidalzellen an der spontanen rhythmischen Aktivität beteiligt sind. / The subiculum plays a key role in processing memory information from the hippocampus to different cortical and subcortical brain regions. Subicular pyramidal cells are classified as regular firing or bursting cells according to their responses to supra-threshold depolarizing current pulses. Synaptic terminals arising from CA1 pyramidal cells do not function as a single compartment but show a specialized synaptic plasticity onto subicular pyramidal cells depending on the discharge properties of the synaptic target. Tetanic stimulation of CA1 axons caused a significantly stronger long-term potentiation (LTP) in bursting cells than in regular firing cells. Postsynaptic bursting was not necessary for the enhanced synaptic potentiation in bursting cells. The LTP in bursting neurons was independent of postsynaptic calcium, induced by presynaptic NR2B-containing autoreceptors and mediated via a adenylyl cylcase-cAMP-dependent signaling cascade. In pilocarpine-treated animals subicular LTP was impaired. A long-lasting increase in synaptic transmission could not be observed after titanic stimulation neither in regular firing cells nor in bursting cells. In human brain slices resected from patients from with drug-resistant temporal lobe epilepsy the subiculum displayed spontaneous rhythmic activity. In sclerotic but also in non-sclerotic hippocampal tissue the subiculum showed cellular and synaptic changes which suffice to generate spontaneous rhythmic activity that is correlated with the occurrence and frequency of interictal discharges recorded in the electroencephalograms of the corresponding patients.

L’épilepsie du lobe temporal (ELT) est une pathologie neurologique sévère dont le fort taux de pharmacorésistance nécessite de nouveaux traitements. Le modèle lithium-pilocarpine modélise les caractéristiques et le développement de l’ELT. L’administration du carisbamate au début de l’épileptogenèse empêche l’apparition de l’ELT dans une sous-population de rats et la remplace par une épilepsie de type absence (ETA). L’évaluation cognitive effectuée durant la phase chronique a permis de distinguer les deux sous-populations : le groupe épilepsie de type absence ne développe pas le déficit cognitif sévère observé dans le modèle lithium pilocarpine. La spectroscopie du 13C n’a pas révélé de différence métabolique majeure entre les deux sous populations traitées, qu’elles développent une ELT ou une ETA. Ce travail souligne que l’administration précoce de carisbamate peut transformer l’ELT en une épilepsie moins sévère et fortement améliorer les comorbidités cognitives qui accompagnent l’ELT. / Temporal lobe epilepsy (TLE) is a severe neurological disease with a high refractory rate, which requires new treatments. The lithium-pilocarpine model allows reproducing human TLE features and development. Carisbamate administration at epileptogenesis onset prevents TLE incidence in a rats’ subpopulation, which is substituted by absence-like epilepsy (ALE). Behavioral and cognitive assessment performed during chronic period allowed differentiating the two subpopulations: ALE group did not develop the severe cognitive impairment shown in the lithium-pilocarpine model. 13C spectroscopy did not show major metabolism difference between the two treated subpopulations, whatever they develop TLE or ALE. This work demonstrates that early carisbamate administration can induce a shift from TLE in a less severe epilepsy form, and can strikingly improve TLE-related cognitive comorbidities.