Caractérisation de la co-organisation nanoscopique des récepteurs glutamatergiques à l'état basal et dans un modèle d'autisme

Abstract : AMPA, NMDA and mGluR5 receptors are responsible of the majority of excitatory currents in glutamatergic synaptic transmission. Controlling the organization and the mobility of these receptors in the synapse, via a combination of lateral diffusion and endo/exocytosis, is essential for the regulation of synaptic transmission intensity. The proteins of the post-synaptic density, such as Homer, Shank and GKAP, regulate the diffusion of these receptors and control their number and organization at the post-synapse. My PhD work consisted of studying the nanoscale organization of AMPA, NMDA and mGluR5 receptors at the post-synapse. As a first step, thanks to the development of different methodological tools, I characterized the organization and dynamic properties of glutamatergic receptors, together with their co-organization within the post-synapse. As a second step, I explored the impact of structural modification of the post-synaptic density on the nano-organization of these receptors. The use of a model of autism spectrum disorder, based on a variation of the scaffold protein Shank3, enabled the study of functional disorganization of glutamate receptors induced by a structural disturbance of the post-synaptic density. This work shows a clustered organization of AMPA and NMDA receptors at the post-synapse, and a homogenous distribution of mGluR5 at their periphery. The AMPARs and NMDARs nanodomains are not co-localized but co-organized, with a tendency for the NMDARs to occupy a central place at the post-synapse. The individual organizational properties of AMPA receptors are not affected by the variation of Shank3 expression, whereas NMDARs and mGluR5 see their synaptic pool affected in this model of autism spectrum disorder. These results provide new evidence on the molecular bases of glutamatergic synaptic transmission in physiological and pathological conditions and propose a new vision of the use of glutamate by synapses.
Document type :
Theses
Complete list of metadatas

Cited literature [187 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-02295016
Contributor : Abes Star <>
Submitted on : Tuesday, September 24, 2019 - 1:02:37 AM
Last modification on : Wednesday, September 25, 2019 - 1:10:38 AM

File

GONCALVES_JULIA_2018.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-02295016, version 1

Collections

Citation

Julia Goncalves. Caractérisation de la co-organisation nanoscopique des récepteurs glutamatergiques à l'état basal et dans un modèle d'autisme. Neurosciences [q-bio.NC]. Université de Bordeaux, 2018. Français. ⟨NNT : 2018BORD0275⟩. ⟨tel-02295016⟩

Share

Metrics

Record views

78

Files downloads

11