Theo GAUVRIT




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2 publication(s) depuis Novembre 2023:


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15/04/2026 | adv sci (weinh)
Diminished Signal-to-Noise Ratio Disrupts Somatosensory Population Encoding and Drives Tactile Hyposensitivity in the Fmr1(-/y) Autism Model.
Semelidou O, Gauvrit T, Vandromme C, Cornier A, Saint-Jean A, Feuvre YL, Ginger M, Frick A
doi: 10.1002/advs.202519479

Abstract:
Touch is essential for interacting with the world, and atypical tactile experience is a core feature of autism that profoundly affects daily life. However, we do not know the neural mechanisms of low-level tactile perception and their alterations in autism. Using a translational forepaw-based perceptual task, we recapitulate the multifaceted tactile features of autistic individuals in the Fmr1(-/y) mouse model of autism, showing reduced detection of low-level vibrotactile stimuli, interindividual variability, and unreliable responses. We reveal that impaired detection decoding in Fmr1(-/y)-hyposensitive mice stems from diminished single-neuron signal-to-noise ratio within layers 2/3 of the primary somatosensory cortex that contributes to weak population encoding of the tactile stimulus and its detection. This manifests as reduced stimulus-dependent neural recruitment, impaired response precision, and disrupted ensemble dynamics. Decreasing neuronal excitability strengthens sensory encoding and restores tactile perception. This work provides a translational framework for probing neuronal-perceptual changes in neurodevelopmental conditions, reveals inter-individual variability in preclinical models, and uncovers the neural basis of tactile hyposensitivity in autism.




Abstract:
Excessive neural variability of sensory responses is a hallmark of atypical sensory processing in autistic individuals with cascading effects on other core autism symptoms but unknown neurobiological substrate. Here, by recording neocortical single neuron activity in a well-established mouse model of Fragile X syndrome and autism, we characterized atypical sensory processing and probed the role of endogenous noise sources in exaggerated response variability in males. The analysis of sensory stimulus evoked activity and spontaneous dynamics, as well as neuronal features, reveals a complex cellular and network phenotype. Neocortical sensory information processing is more variable and temporally imprecise. Increased trial-by-trial and inter-neuronal response variability is strongly related to key endogenous noise features, and may give rise to behavioural sensory responsiveness variability in autism. We provide a novel preclinical framework for understanding the sources of endogenous noise and its contribution to core autism symptoms, and for testing the functional consequences for mechanism-based manipulation of noise.