Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice’s behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors.

中文翻译：

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皮层限制性删除 Foxp1 会损害自闭症小鼠模型中的桶形成并诱导异常的触觉反应

许多患有自闭症谱系障碍 (ASD) 的儿童和青少年表现出触摸防御或回避（过敏），或通过触摸人或物体进行感官寻求（过敏）。在缺乏 ASD 相关基因的小鼠中也发现了异常的感觉反应。触觉感觉信息通常由沿着丘脑传播到初级体感皮层的体感系统处理。然而，触觉感觉异常背后的神经生物学尚未完全了解。在本研究中，我们采用皮质特异性 Foxp1 敲除 (Foxp1-cKO) 小鼠作为自闭症模型。通过粘合剂去除测试来测量触觉感觉缺陷。分别通过胡须滋扰测试和c-Fos免疫荧光进一步评估小鼠的行为和神经活动。我们还通过高尔基染色和免疫荧光研究了初级体感皮层的树突棘和桶的形成。Foxp1-cKO 小鼠对触觉环境的反应迟缓。然而，在反复刺激胡须后，小鼠表现出回避行为和过度反应，类似于战斗或逃跑反应。与野生型相比，c-Fos 在 cKO 小鼠的基底外侧杏仁核中被激活，但在初级体感皮层的第四层中没有被激活。此外，皮质神经元中的 Foxp1 缺陷改变了树突发育，减少了树突棘的数量，并扰乱了体感皮层的桶形形成，表明体感处理受损可能是异常触觉反应的基础。目前尚不清楚丘脑皮质连接缺陷如何引起过度反应。未来需要进行电生理记录实验来分析丘脑-皮质-杏仁核回路在杏仁核去抑制中的作用以及自闭症小鼠模型中增强的恐惧反应。Foxp1-cKO 小鼠存在触觉缺陷，同时表现出过度反应，这可能代表杏仁核控制的恐惧和情绪反应。这项研究提供了自闭症遗传小鼠模型中丘脑皮质连接减少的解剖学证据，并证明大脑皮层可能是非典型感觉行为的起源。