Venue: Centre Broca
Floriane Uyttersprot
Team Groc – IINS
Thesis supervisor: Julien Dupuis
Title
Exploring the molecular determinants of behavioral changes induced by ketamine at the nanoscale
Abstract
NMDA glutamate receptors (NMDAR) are major actors of excitatory neurotransmission and synaptic plasticity. Their synaptic organization plays a key role in these processes and is tightly and dynamically regulated. Consequently, pathological alterations of this organization have been associated with severe neuropsychiatric disorders. Thus, NMDAR synaptic organization could represent a valuable therapeutic target. In this work, we show that ketamine, a non-competitive NMDAR antagonist, enhances synaptic trapping of the receptors and thereby mitigates anxiety and depression symptoms caused by autoantibodies from patients with autoimmune encephalitis. Furthermore, our results suggest that the antidepressant action of ketamine involves a rewiring or brain networks that could involve a subtype-dependent reorganization of synaptic NMDAR. Together, these results open new therapeutic perspectives for the treatment of mental disorders associated with NMDAR hypofunction.
Keywords: NMDA receptor, ketamine, nanoscale organization, depression
Publication
Villéga, F. et al.
Ketamine alleviates NMDA receptor hypofunction through synaptic trapping.
Neuron S0896627324004902 (2024)
doi:10.1016/j.neuron.2024.06.028.
Jury
- Stéphane OLIET – Directeur de Recherche, Université de Bordeaux – Président
- Ana Luisa CARVALHO – Professeure, Université de Coimbra – Rapportrice
- Mme. Julie PERROY – Directrice de Recherche, Université de Montpellier – Rapportrice
- Thomas FRERET – Professeur, Université de Caen – Examinateur
- Julien DUPUIS – Chargé de Recherche, Université de Bordeaux – Directeur de thèse