The developmental timing of spinal touch processing alterations predicts behavioral changes in genetic mouse models of autism spectrum disorders.

Autor: Tasnim A; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA., Alkislar I; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA., Hakim R; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA., Turecek J; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA., Abdelaziz A; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA., Orefice LL; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Ginty DD; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA. david_ginty@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2024 Mar; Vol. 27 (3), pp. 484-496. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1038/s41593-023-01552-9
Abstrakt: Altered somatosensory reactivity is frequently observed among individuals with autism spectrum disorders (ASDs). Here, we report that although multiple mouse models of ASD exhibit aberrant somatosensory behaviors in adulthood, some models exhibit altered tactile reactivity as early as embryonic development, whereas in others, altered reactivity emerges later in life. Additionally, tactile overreactivity during neonatal development is associated with anxiety-like behaviors and social behavior deficits in adulthood, whereas tactile overreactivity that emerges later in life is not. The locus of circuit disruption dictates the timing of aberrant tactile behaviors, as altered feedback or presynaptic inhibition of peripheral mechanosensory neurons leads to abnormal tactile reactivity during neonatal development, whereas disruptions in feedforward inhibition in the spinal cord lead to touch reactivity alterations that manifest later in life. Thus, the developmental timing of aberrant touch processing can predict the manifestation of ASD-associated behaviors in mouse models, and differential timing of sensory disturbance onset may contribute to phenotypic diversity across individuals with ASD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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