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.

在患有自闭症谱系障碍 (ASD) 的个体中经常观察到体感反应性的改变。在这里，我们报告说，尽管多种 ASD 小鼠模型在成年期表现出异常的体感行为，但一些模型早在胚胎发育时就表现出触觉反应性的改变，而在其他模型中，反应性的改变在生命后期才出现。此外，新生儿发育期间的触觉过度反应与成年期的焦虑样行为和社会行为缺陷有关，而晚年出现的触觉过度反应则不然。电路中断的位置决定了异常触觉行为的时间，因为周围机械感觉神经元的反馈改变或突触前抑制导致新生儿发育期间的触觉反应异常，而脊髓前馈抑制的中断导致触觉反应性改变，并在以后的发育过程中表现出来。生活。因此，异常触摸处理的发育时间可以预测小鼠模型中 ASD 相关行为的表现，而感觉障碍发作的差异时间可能有助于 ASD 个体的表型多样性。