The developmental timing of spinal touch processing alterations and its relation to ASD-associated behaviors in mouse models.
The developmental timing of spinal touch processing alterations and its relation to ASD-associated behaviors in mouse models.
复制标题
小鼠模型中脊柱触觉处理改变的发育时间及其与 ASD 相关行为的关系。
DOI：
10.1101/2023.05.09.539589
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ginty,DavidD
中科院分区：
文献类型：
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作者：
Tasnim,Aniqa;Alkislar,Ilayda;Hakim,Richard;Turecek,Josef;Abdelaziz,Amira;Orefice,LaurenL;Ginty,DavidD
在自闭症谱系障碍（ASD）患者中经常观察到体感反应的改变。在这里，我们报告说，虽然多个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，反应性的改变出现在生命的后期。此外，新生儿发育期间的触觉过度反应与成年后的焦虑样行为和社会互动缺陷有关，而在生命后期出现的触觉过度反应则无关。回路中断的位点决定了异常触觉行为的发生时间：外周机械感觉神经元的反馈或突触前抑制改变会导致新生儿发育期间的异常触觉反应，而脊髓前馈抑制的中断会导致在以后的生活中表现出的触觉反应性改变。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，感觉障碍发作的不同时间可能有助于ASD个体的表型多样性。
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.