Biology subjects

Desmedt, A.

Publications and source records attributed to Desmedt, A..

4 recordsLinked to original sources

bioRxiv2026

Anterior cingulate cortex engram drives post traumatic stress disorder-like memory impairments in a rodent model of traumatic fear

Fear memories in post-traumatic stress disorder are marked by persistent cue-driven recollection and impaired contextual recall, yet the engram organization underlying this maladaptive state remains unclear. Here we used a rodent model combining contextual fear conditioning with systemic corticosterone to mimic trauma-associated glucocorticoid exposure. This paradigm generated a PTSD-like phenotype characterized by hypermnesia for a trauma-related but irrelevant (non-predictive of the threat) cue and contextual amnesia. Activity-dependent tagging and reactivation mapping revealed that traumatic memory is supported by a regionally dysregulated engram pattern, with enhanced recruitment of the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), and reduced engagement of the dentate gyrus (DG). These changes persisted over time and correlated with the severity of the behavioral phenotype. Chemogenetic inhibition of ACC engram cells abolished traumatic memory expression, restored contextual recall, and normalized engram reactivation across DG and BLA. In contrast, inhibition of randomly tagged ACC or hippocampal populations had no such effect, indicating that the ACC engram is specifically required for traumatic memory expression. Together, these findings show that PTSD-like memory is not simply an amplified fear trace, but a distinct maladaptive engram state distributed across cortical-hippocampal- amygdalar circuits.

neuroscience↗

bioRxiv2025

Stress-induced plasminogen activator inhibitor-1 (PAI-1) as a blood biomarker and brain risk factor for PTSD

Post-traumatic stress disorder (PTSD) is a severe stress-related psychiatric condition triggered by traumatic life-threatening events, characterized notably by an altered memory profile. Although clinically well-documented, no specific biomarker exists. This translational study identifies plasminogen activator inhibitor-1 (PAI-1) as a brain risk factor for PTSD, thereby supporting its potential as a blood-derived biomarker. Mice with genetically ablated PAI-1 were protected from developing a PTSD-like memory profile. Conversely, mice exhibiting PTSD-like cognitive impairment showed increased blood PAI-1 levels, correlating with their profile severity. In the brain, PAI-1 levels were specifically increased in the dorsal hippocampus, a key region for cognitive functions and in the etiology of PTSD. Finally, a longitudinal study of soldiers revealed that those developing PTSD symptoms exhibit rising blood PAI-1 levels over a 12-month period. Its significant association with various indicators of PTSD-related psychological distress attests to PAI-1s potential as a blood biomarker and brain therapeutic target for PTSD.

neuroscience↗

bioRxiv2024

The correct temporal connectivity of the DG CA3 circuits involved in declarative memory processes depends on Vangl2-dependent planar cell polarity signaling

In the hippocampus, dentate gyrus granule cells connect to CA3 pyramidal cells via their axons, the mossy fibers (Mf). The synaptic terminals of Mfs (Mf boutons, MfBs) form large and complex synapses with thorny excrescences (TE) on the proximal dendrites CA3 pyramidal cells (PCs). MfB/TE synapses have distinctive "detonator" properties due to low intitial release probability and large presynaptic facilitation. The molecular mechanisms shaping the morpho-functional properties of MfB/TE synapses are still poorly understood, though alterations in their morphology are associated with Down syndrome, intellectual disabilities, and Alzheimers disease. Here, we identify the core PCP gene Vangl2 as essential to the morphogenesis and function of MfB/TE synapses. Vangl2 colocalises with the presynaptic heparan sulfate proteoglycan glypican 4 (GPC4) to stabilise the postsynaptic orphan receptor GPR158. Embryonic loss of Vangl2 disrupts the morphology of MfBs and TEs, impairs ultrastructural and molecular organisation, resulting in defective synaptic transmission and plasticity. In adult, the early loss of Vangl2 results in a number of hippocampus-dependent memory deficits including characteristic flexibility of declarative memory, organisation and retention of working/ everyday-like memory. These deficits also lead to abnormal generalisation of memories to salient cues and diminished ability to form detailed contextual memories. Together, these results establish Vangl2 as a key regulator of DG-CA3 connectivity and functions. HighlightsO_LIVangl2 is a key regulator of MfB/TE synapses morphogenesis and plasticity in CA3 C_LIO_LIVangl2-mediated GPC4-GPR158 interaction maintains MfB-TE pre-synaptic morphology and function C_LIO_LIVangl2 deletion affects declarative memory in adult mice C_LIO_LIVangl2 function is necessary for contextual learning and its loss leads toa maladaptive fear memory for salient cues C_LI

neuroscience↗

bioRxiv2021

Autism Spectrum Disorder is a Risk Factor for PTSD-like Memory Formation

A rising concern in Autism Spectrum Disorder (ASD) is the heightened sensitivity to stress and trauma, the potential consequences of which have been overlooked, particularly upon the severity of the ASD traits. This study investigated the predisposition to, and impact of, Post-Traumatic Stress Disorder (PTSD) in ASD. We first demonstrated a reciprocal relationship between the two disorders and revealed that exposure to a mild stressful event induces PTSD-like memory in four mouse models of ASD. We also establish an unanticipated consequence of stress in this condition, showing that the formation of PTSD-like memory leads to the aggravation of the core traits associated with ASD. Such a susceptibility to developing PTSD-like memory in ASD stemmed from hyperactivation of the prefrontal cortex and altered fine-tuning of parvalbumin interneuron firing. We show that this traumatic memory can be treated by recontextualization, reducing the deleterious effects on the core symptoms of ASD. Overall, this study reveals multi-level neurobiological mechanisms that explain the increased vulnerability to develop PTSD in ASD. It provides a framework for future examination of the impact of PTSD-like memory in autism and offers new directions toward behavioral therapeutic interventions targeting traumatic memory in ASD.

neuroscience↗