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Theses

Study of cerebellar synaptic deficits in two rodent models of schizophrenia

Abstract : Schizophrenia is a synaptopathy, a disease of the synapse. However, the developmental mechanisms leading to the formation and fine-tuning of synaptic circuitry have been poorly studied. The olivo-cerebellar network, due to its stereotypical synaptic architecture, is a useful model for studying these mechanisms. In addition, although initially known for its motor functions, the cerebellum is also involved in more complex cognitive tasks, and may play a role in the etiology of schizophrenia. While in the LgDel genetic mouse model of schizophrenia, cerebellar synaptic architecture seem unaffected, the environmental neonatal pharmacological model Phencyclidine (PCP) showed specific morphological alterations of the climbing fiber, one of the two excitatory afferents of the Purkinje cell. These deficits are associated with an activity-dependent deregulation of the expression of genes coding for membrane and secreted proteins, including the gene encoding the secreted protein CTGF, a protein that interacts with several actors of synaptic development. The results of this thesis suggest that an environmental perturbation of neuronal activity during a critical period of development could disrupt the establishment of the synaptic microcircuitry in the cerebellum, potentially playing a role in neurodevelopmental disorders such as schizophrenia.
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https://tel.archives-ouvertes.fr/tel-03378196
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Submitted on : Thursday, October 14, 2021 - 3:07:09 PM
Last modification on : Wednesday, November 17, 2021 - 12:31:53 PM

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VELEANU_Maxime_2020.pdf
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  • HAL Id : tel-03378196, version 1

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Maxime Veleanu. Study of cerebellar synaptic deficits in two rodent models of schizophrenia. Neurons and Cognition [q-bio.NC]. Sorbonne Université, 2020. English. ⟨NNT : 2020SORUS362⟩. ⟨tel-03378196⟩

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