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Cette thèse avait pour objectif d’étudier le rôle du circuit composé de l’hippocampe (Hip), du cortex préfrontal médian (mPFC) et des noyaux reuniens et rhomboïde (ReRh) du thalamus dans les processus cognitifs qui sous-tendent la mémoire spatiale chez le Rat. Nous avons montré que les noyaux ReRh pourraient être impliqués dans la consolidation systémique, mécanisme nécessaire à la persistance des souvenirs et nécessitant un dialogue hippocampo-cortical. Nous avons mis en évidence que l’activité neuronale du mPFC durant le rappel d’une mémoire ancienne dépend des noyaux ReRh, ainsi que l’implication de ces noyaux dans une tâche de mémoire spatiale (dépendante de l’Hip) nécessitant une flexibilité comportementale (impliquant le mPFC). Enfin, nous avons montré un rôle du mPFC dans le rappel d’une mémoire spatiale récente. Ces résultats mettent en évidence l’importance de ce circuit hippocampo-cortico-thalamique dans le traitement et la persistance des informations spatiales chez le Rat. / This thesis aimed to investigate the role of a circuit encompassing the hippocampus (Hip), the medial prefrontal cortex (mPFC) and the reuniens and rhomboid nuclei (ReRh) of the thalamus in cognitive processes underlying spatial memory in rats. We first showed that ReRh nuclei may be involved in systemic consolidation, a mechanism necessary for memory persistence and requiring hippocampal-cortical interactions. We confirmed these findings in a second study showing that mPFC neuronal activity during recall of a remote spatial memory depends on ReRh thalamic nuclei. We also showed the involvement of the ReRh nuclei in a mnemonic task requiring the use of both spatial information (dependent on the Hip) and behavioral flexibility (involving the mPFC). Finally, we found a role of the mPFC in the recall of recent spatial memory. Taken together, these results highlight the importance of a hippocampo-cortico-thalamic circuit in the processing and persistence of spatial information in the Rat.

Ce travail visait à évaluer le potentiel d’une méthodologie innovante récemment adaptée à la Souris sur la base de tests neuropsychologiques utilisés en clinique humaine. Après optimisation de 3 tâches (PAL, VMCL, PVD) ciblant différentes fonctions cognitives chez l’animal, nos études ont établi : (1) l’existence possible d’interférences proactives lors d’apprentissages consécutifs ; (2) l’absence de déficit d’acquisition chez les souris de la lignée Tg2576 (modèle transgénique de la maladie d’Alzheimer), quelle que soit l’étendue de la charge amyloïde ; (3) l’implication spécifique du striatum dorsal lors de l’acquisition des tâches de VMCL et PAL, et celle de l’hippocampe lors du rappel de cette dernière tâche. Ces derniers résultats suggèrent qu’en dépit des efforts déployés pour s’assurer du caractère translationnel d’une tâche cognitive dans le paradigme du touchscreen, certaines adaptations inhérentes à chaque espèce influencent profondément les bases neurobiologiques associées. / This thesis work aimed to specify the potential of an innovative methodology latterly adapted in mice from neuropsychological tasks used in Humans. After the optimization of 3 assays (PAL, VMCL, PVD) taxing various cognitive functions in animals, different behavioral studies have gradually revealed: (1) the putative existence of proactive interferences over consecutive learnings in touchscreen tasks; (2) no acquisition deficit in Tg2576 mice (a transgenic model of Alzheimer’s Disease) in these paradigms, whatever the amyloid load considered; (3) the specific involvement of the dorsal striatum during the acquisition of VMCL and PAL tasks and the key role of the hippocampus during the recall of the latter task. As exemplified by the PAL task, our results suggest that despite momentous efforts in order to ensure the translational feature of touchscreen cognitive tasks, certain adaptations inherent to each species deeply influence the nature of underlying neurobiological substrates.

The purpose of this thesis was to develop methodology by which treatments for the cognitive impairments in Huntington's disease (HD) could be tested. As such, the thesis focused mainly on evaluating rats with quinolinic acid (QA) lesions of the striatum, as this manipulation mimics some aspects of the neural damage in Huntington's disease, to try to identify cognitive deficits of HD resulting from cell loss in the striatum. In the first part (Chapters 3-5), the role of the striatum in implicit memory was investigated. Chapter 3 compared the performance of rats and humans on a reaction time task that evaluated implicit memory by presenting visual stimuli with differing probabilities which change over time. Although rats made higher percentage of incorrect responses and late errors, both groups showed a similar pattern of reaction times. Chapter 4 investigated whether implicit memory (the computation of probabilities to predict the location of a stimulus) was affected by selective blockade of dopaminergic transmission at the D1 or D2 receptors by SCH-23390 and raclopride, respectively. Reaction times were slower with SCH-23390 and raclopride, but only SCH-23390 reduced errors to the least probable target location. Chapter 5 used the same task to evaluate implicit memory in rats with QA lesions of the dorsomedial striatum (DMS). Implicit memory was not affected by lesions of the DMS, which suggested that once a task that requires implicit memory has been learned, the DMS was not involved in sustaining the performance of the task. The second part of this thesis (Chapter 6), explored the contribution of the DMS in habit formation. DMS lesioned rats did not show habitual responding, and were not impaired in learning a new goal-directed behaviour. The third part (Chapters 7 and 8), investigated the role of the dorsal striatum in reversal learning, attentional set-formation, and set-shifting. Dorsal striatum lesioned rats were not impaired in reversal learning, but had a diminished shift-cost, which suggested that dorsal striatum lesions disrupted the formation of attentional sets. These results showed that although QA lesions of the dorsal striatum mimic some aspects of the neural damage in HD, they did not result in the same cognitive deficits observed in patients with HD, at least using the tasks presented in this thesis. However, other animal models of HD could be evaluated using the different tasks presented in this thesis to continue the search of a reliable animal model of HD in which treatments for the disease could be evaluated.