Étude des atypies sensorielles néonatales dans un modèle murin d’autisme associé à la mutation du gène Magel2
Ugo Zayan
Equipe “Empreintes périnatales et troubles du neurodéveloppement”

Abstract
Sensory atypias are among the earliest detectable manifestations of autism spectrum disorders (ASD), yet the developmental origins and cortical bases of these alterations remain poorly understood. In this study, we combine behavioral, pharmacological, and neurophysiological approaches to characterize early thermosensory processing and its disruption in a genetic mouse model of ASD (Magel2). We show that Magel2-KO pups exhibit hyporeactivity to cool stimuli, despite intact autonomic thermoregulation. This sensory deficit is linked to dysfunction of the oxytocinergic system: chemogenetic inactivation of oxytocin neurons in wild-type pups reproduces the phenotype of mutants, while intranasal administration of oxytocin restores in the mutant the altered behavioral responses. Additionally, in vivo imaging and electrophysiological recordings reveal that cool stimuli evoke lateralized cortical responses in the primary somatosensory cortex as early as the first postnatal week. In Magel2 mutants, this thermosensory encoding is disrupted, showing spatial disorganization and cortical hyperexcitability. Altogether, these results provide the first evidence for the early presence of functional cortical maps for thermosensation and suggest that ASD-related thermosensory alterations originate from central mechanisms, with oxytocin emerging as a potential therapeutic target from the earliest stages of life.

Jury
Mario CARTA, Rapporteur – IINS, Bordeaux
Julie LE MERRER, Rapportrice – iBraiN, Tours
Rochelle ACKERLEY, Examinatrice – CRPN, Marseille
Laurie GALVAN, Examinatrice – Nîmes Université
Christophe PORCHER, Président – Inmed, Marseille
Valéry MATARAZZO, Directeur de thèse – Inmed, Marseille

Wednesday 16 July 2025 at 2pm – Inmed conference room