Thesis defense – Flávia Simões

On November 27, 2026 at 14:00

Venue: Centre Broca

Language of defense: english

Flávia Simões

IINS/Neurocentre Magendie

Thesis supervisors: Olivier Nicole and Sophie Tronel

Title

Deciphering the neural mechanisms underlying traumatic fear memory: from brain-wide network dysfunction to the altered engram ensemble

Abstract

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that may develop following exposure to a traumatic event. It has a lifetime prevalence of around 4% in the general population, affecting up to 24% of people that underwent trauma. Diagnostic symptoms include intrusive thoughts, avoidance of trauma-related stimuli, negative alterations in mood and heightened arousal, all of which significantly impair the quality of life of patients. Beyond these well-recognized symptoms, PTSD is also associated with a paradoxical memory profile characterized by an emotional hypermnesia for salient cues while displaying declarative amnesia for events surrounding the trauma. Notably, the neurobiological mechanisms supporting these memory impairments remains largely unexplored. Using a rodent model that reproduces this PTSD-like memory phenotype, we investigated the mechanisms supporting maladaptive traumatic memory across multiple levels of organization, from brain-wide functional networks to neuronal engrams and molecular determinants of memory malleability. At the systems level, brain-wide activity mapping revealed that normal and PTSD-like fear memories rely on distinct functional network organizations during both consolidation and retrieval. PTSD-like memory was associated with a less dense and less efficient functional network, together with enhanced recruitment of cortical, hypothalamic and amygdalar regions compared with adaptive fear memory. These findings suggest that traumatic memory is not simply supported by stronger activation of individual structures, but by a broader reorganization of the brain-wide network underlying memory expression. At the cellular level, we next aimed at dissecting the neuronal ensembles particularly involved in memory expression, the engram population. While extensively described for normal fear memory processes, the traumatic memory engram stays undescribed. Using activity-dependent neuronal tagging combined with targeted manipulation, we identified an abnormal cortical-amygdalar engram hyperactivation associated with traumatic memory expression. Inhibition of this ensemble prevents expression of traumatic fear, while also normalizing the related hippocampal and amygdalar engram activity, supporting the idea that traumatic memory is encoded within a distributed and functionally coordinated engram network. Because PTSD patients display impaired extinction and reduced capacity to update traumatic memories—both key targets of current therapies—we examined whether our model reflects these deficits. PTSD-like memory showed impaired extinction learning, together with resistance to pharmacological disruption of reconsolidation. Given the role of N-Methyl-D-Aspartate Receptors (NMDAR) in memory malleability, we targeted cortical GluN2A-containing NMDAR. 5 Reducing GluN2A-dependent signaling before memory reactivation restored the susceptibility of traumatic memory to reconsolidation blockade, indicating that NMDAR subunit composition can critically regulate the transition between memory stability and malleability. Altogether, by using a multiscale characterization of maladaptive traumatic memory, our findings support the view that pathological traumatic memory arises not simply from excessive fear, but from abnormal stabilization and organization of distributed memory networks.

Keywords: Memory; Post-traumatic stress disorder; Engram; Functional connectivity

 

Jury

  • Olivier NICOLE, Chargé de recherche, CNRS – Thesis supervisor
  • Sophie TRONEL, Chargée de recherche, CNRS – Thesis supervisor
  • Harm KRUGERS , Associate Professor, University of Amsterdam – Spokesperson
  • Amy MILTON, Professor, University of Cambridge – Spokesperson
  • Gisella VETERE Professor, ESPCI Paris – Examinator
  • Guillaume FERREIRA Directeur de recherche, University of Bordeaux – President of the jury
  • Aline Desmedt, Professor, University of Bordeaux – Invited

Publications

Anterior cingulate cortex engram drives Post traumatic stress disorder-like memory impairments in a rodent model of traumatic fear
Flávia V. Simões, Lorenzo Baltimore, Zora Pelloquin-Mvogo, Laurent Groc, Aline Desmedt, Olivier Nicole, Sophie Tronel.
PrePrint bioRXiv. 2026-09-04.
10.64898/2026.09.01.748515 – Fiche

  • Place
    Centre Broca
  • Dates
    On November 27, 2026 at 14:00
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