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, il faut prendre ses distances avec cette approche hiérarchisante consistant à étudier une espèce peu évoluée pour comprendre une espèce plus évoluée. Au contraire, il faut passer d'un paradigme d'étude de modèles animaux à l'étude d'animaux modèles dans un paradigme trans-espèces. En d'autres termes il faut croiser les études sur différentes espèces apportant chacune des données d, 2007.
, ce en tenant compte des différences inter-espèces qui ont une valeur informative. Ceci fait écho au programme RDoC promouvant la recherche sur phénotypes intermédiaires et non syndromes cliniques catégoriels
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, Cette observation phénoménologique a conduit à explorer l'idée que les patients souffrant de TOC présentent un déficit de flexibilité cognitive ; c'est-à-dire de leur capacité à s'adapter aux changements environnementaux. Ainsi, l'objectif était double : tester l'hypothèse d'un déficit de flexibilité cognitive sous-tendant les comportements compulsifs et explorer leurs bases neurobiologiques chez les patients et un modèle animal de compulsion, les souris Sapap3 KO. Nous avons ainsi développé une tâche de renversement de l'apprentissage similaire dans les deux espèces, et observé que seul un sous-groupe de sujets compulsifs, ce dans les deux espèces, présentaient des performances altérées. Ce déficit trans-espèces n'était pas corrélé à la sévérité des comportements compulsifs et se traduisait non par une plus grande tendance à la persévération après renversement des contingences, mais par une plus grande labilité dans leurs réponses après renversement. La suite de ce travail a consisté à explorer les bases neurales de la flexibilité cognitive et son lien avec la compulsion en modulant les circuits cortico-subthalamiques à la fois chez les patients (par stimulation cérébrale profonde) et les souris Sapap3 KO (par modulation pharmacologique et stimulation optogénétique) pendant la réalisation de la tâche, Le trouble obsessionnel-compulsif (TOC) se caractérise par des obsessions (idées intrusives) et des compulsions (comportements répétitifs exécutés au travers de rituels rigides
, Mots clés : [TOC ; Comportement compulsif
, We thus developed a similar reversal learning task in both species, and observed that only a subgroup of compulsive subjects in both species were impaired. This impairment did not result in a greater perseveration after reversal, but in a greater response lability in reversal condition. Moreover, this impairment did not correlate with the severity of compulsive behaviors. The next step in this work was to explore the neural bases of cognitive flexibility and its link with compulsion by modulating cortico-subthalamic circuits in both patients (by deep brain stimulation) and Sapap3 KO mice (by pharmacological modulation and optogenetic stimulation) during task completion, Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive ideas) and compulsions (repetitive behaviors performed through rigid rituals)