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Neurogenèse adulte hippocampique : Rôle fonctionnel dans la mémoire épisodique et recrutement des nouveaux neurones lors de la mémorisation

Abstract : Adult hippocampal neurogenesis plays a critical role in hippocampal-dependent memory, however its role in complex forms of memory such as episodic memory has not as yet been explored. The work presented in this thesis focuses on the issue of the involvement of newborn hippocampal neurons in long term episodic memory. We developed a new episodic memory task based on the presentation of occasional episodes allowing rats to encode “What – Where – In which context” information. We show for the first time that rats are able to remember on the long term brief past episodes of life and to use their episodic memory in a flexible manner. The characterization of retention profiles allows us to identify individual abilities in the recollection of the various elements of the memory and shows that episodic memory recall requires the integrity of the hippocampus and involves a hippocampo-cortical network, the activation of which correlates with recall performance. Performance of rats subjected to focal irradiation of the hippocampus shows that adult hippocampal neurogenesis contributes significantly to the consolidation and faithful recall of episodic memory. These results are discussed in the context of the implication of hippocampal newborn neurons in the resolution of memories of occasional events in order to discriminate different, but closely related episodes of life in relation to pattern separation and pattern completion functions of the hippocampus. Furthermore, the molecular mechanisms underlying the recruitment of newborn hippocampal neurons by learning remain to date unknown. We investigated the role of Zif268, an immediate early gene known to play an essential role in memory processes, and show that this gene plays a crucial role in the selection and recruitment of newborn hippocampal neurons by learning during their critical period of integration in hippocampal neural networks. Overall, this work brings new knowledge on the contribution of newborn hippocampal neurons to memory processes in a highly demanding cognitive situation based on the encoding of an integrated and high-resolution representation of complex occasional events, and on the mechanisms underlying their recruitment.
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Alexandra Gros. Neurogenèse adulte hippocampique : Rôle fonctionnel dans la mémoire épisodique et recrutement des nouveaux neurones lors de la mémorisation. Neurosciences [q-bio.NC]. Université Paris Sud - Paris XI, 2015. Français. ⟨NNT : 2015PA11T051⟩. ⟨tel-02927787⟩

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