Thsesis defense – Simon Lecomte

On November 28, 2025 at 14:30

Venue: BBS

Simon Lecomte
Team: Synapses et circuits neuronaux

Thesis supervisor: Christophe Mulle

Title

“Impact of FMRP deletion on presynaptic mechanisms at mf-CA3 synapse”

Abstract

Fragile X syndrome (FXS), the most common inherited form of intellectual disability and a major cause of autism spectrum disorder, results from silencing of the Fmr1 gene encoding the RNA-binding protein, FMRP. While most research has focused on dendritic and postsynaptic mechanisms, emerging evidence suggests a presynaptic role of FMRP, particularly through cAMP-dependent signaling pathways. This project investigates how loss of FMRP affects presynaptic mechanisms in the CA3 region of the hippocampus, with a specific emphasis on cAMP–protein kinase A (PKA) signaling. Using patch-clamp electrophysiology and imaging in acute and fixed mouse hippocampal slices with targeted genetic mutations in dentate gyrus cells, I show that presynaptic loss of FMRP disrupts mossy fiber–CA3 synaptic transmission. My results indicate a deregulation of cAMP–PKA signaling and altered presynaptic calcium-dependent mechanisms, providing new insights into the presynaptic contribution of FMRP to synaptic function in FXS.

Keywords: FMRP, hippocampus, mossy fiber, presynapse, patch-clamp

Publication

Marneffe, C., Moreira-de-Sá, A., Lecomte, S., Erhardt, A., & Mulle, C. (2025). Short term plasticity at hippocampal mossy fiber synapses. Neuroscience, 578, 105-117. (ainsi que diverses publications dans le journal étudiant brainstorm, et podcast “Thèse et vous”)

Jury

  • Andreas Frick (Neurocentre Magendie, Bordeaux, président du jury, examinateur)
  • Ingrid Bureau (INMED, Marseille, rapportrice)
  • Pierre Vincent (IGF, Montpellier, rapporteur)
  • Joana Lourenço (ICM, Paris, examinatrice)
  • Yann Humeau (FMI, Bâle, invité)

  • Place
    BBS
  • Dates
    On November 28, 2025 at 14:30
Share