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Endogenous noise of neocortical neurons correlates with atypical sensory response variability in the Fmr1−/y mouse model of autism

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  • Arjun A. Bhaskaran

    (INSERM, U1215 Neurocentre Magendie
    University of Bordeaux
    University of British Columbia)

  • Théo Gauvrit

    (INSERM, U1215 Neurocentre Magendie
    University of Bordeaux)

  • Yukti Vyas

    (INSERM, U1215 Neurocentre Magendie
    University of Bordeaux)

  • Guillaume Bony

    (INSERM, U1215 Neurocentre Magendie
    University of Bordeaux)

  • Melanie Ginger

    (INSERM, U1215 Neurocentre Magendie
    University of Bordeaux)

  • Andreas Frick

    (INSERM, U1215 Neurocentre Magendie
    University of Bordeaux)

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.

Suggested Citation

  • Arjun A. Bhaskaran & Théo Gauvrit & Yukti Vyas & Guillaume Bony & Melanie Ginger & Andreas Frick, 2023. "Endogenous noise of neocortical neurons correlates with atypical sensory response variability in the Fmr1−/y mouse model of autism," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43777-z
    DOI: 10.1038/s41467-023-43777-z
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    References listed on IDEAS

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    1. Matthew E. Larkum & J. Julius Zhu & Bert Sakmann, 1999. "A new cellular mechanism for coupling inputs arriving at different cortical layers," Nature, Nature, vol. 398(6725), pages 338-341, March.
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