The developmental timing of spinal touch processing alterations and its relation to ASD-associated behaviors in mouse models

ABSTRACT Altered somatosensory reactivity is frequently observed among individuals with autism spectrum disorders (ASDs). Here, we report that while multiple mouse models of ASD exhibit aberrant somatosensory behaviors in adulthood, some models exhibit altered tactile reactivity as early as embryonic development, while in others, altered reactivity emerges later in life. Additionally, tactile over-reactivity during neonatal development is associated with anxiety-like behaviors and social interaction deficits in adulthood, whereas tactile over-reactivity that emerges later in life is not. The locus of circuit disruption dictates the timing of aberrant tactile behaviors: altered feedback or presynaptic inhibition of peripheral mechanosensory neurons leads to abnormal tactile reactivity during neonatal development, while 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.