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Etude du rôle de VGLUT3, un transporteur vésiculaire du glutamate atypique, dans l'amygdale cérébrale dans le contexte de peur acquise

Abstract : Post-Traumatic Stress Disorder (PTSD) is an anxiety-like disorder usually triggered by a traumatic experience. Brain structures such as the prefrontal cortex, the hippocampus or the amygdala belonging to the learning and emotional memories network, are particularly affected. As this network is extremely well conserved during evolution, acquisition and consolidation of aversive memories can be studied by a Pavlovian fear conditioning paradigm in rodents. Our team has identified a strong expression of the vesicular glutamate transporter, VGLUT3 in the basolateral amygdala (BLA). VGLUT3 allows, like all vesicular transporters, neurotransmitter internalization, here the glutamate in synaptic vesicles. VGLUT3 is atypical because of its distribution and its functions. The aim of my work is to identify the neuronal population expressing VGLUT3 in the amygdala as well as its role in processing aversive memories. The anatomical characterisation revealed: 1/ VGLUT3 mRNA in BLA GABAergic interneurons, 2/ VGLUT3 protein in cholinergic and serotoninergic terminals in the BLA, identifying two populations of projecting neurons expressing VGLUT3. To decipher the functional role of VGLUT3, we used viral and genetic approaches to ablate VGLUT3 either in GABAergic, serotoninergic or cholinergic terminals. Mice lacking VGLUT3 constitutively show contextual generalization and rapid extinction. Specific inactivation of VGLUT3 in BLA impairs aversive memories, shedding light on a specific role of VGLUT3 in modulating fear responses through its presence in BLA interneurons. These new data will be discussed in the context of PTSD and would open a new direction for the development of therapeutic treatment.
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Nida Chabbah. Etude du rôle de VGLUT3, un transporteur vésiculaire du glutamate atypique, dans l'amygdale cérébrale dans le contexte de peur acquise. Neurosciences [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066280⟩. ⟨tel-02324611⟩



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