Somatosensory cortex hyperconnectivity and impaired whisker-dependent responses in Cntnap2-/- mice
Somatosensory cortex hyperconnectivity and impaired whisker-dependent responses in Cntnap2-/- mice
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DOI：
10.1016/j.nbd.2022.105742
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发表时间：
2022-04-28
影响因子：
6.1
通讯作者：
Bozzi, Yuri
中科院分区：
文献类型：
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作者：
Balasco, Luigi;Pagani, Marco;Bozzi, Yuri
感觉异常是自闭症谱系障碍 (ASD) 的常见特征。自闭症患者的触觉反应能力发生了改变，反应能力低下与自闭症谱系障碍核心症状的严重程度有关。同样，缺乏 ASD 相关基因的小鼠也出现了感觉异常。 CNTNAP2 的功能丧失突变会导致皮质发育不良-局灶性癫痫综合征 (CDFE) 和自闭症。同样，Cntnap2-/- 小鼠表现出与人类 ASD 核心症状相关的癫痫和缺陷，被认为是研究 ASD 的可靠模型。 Cntnap2-/- 小鼠大脑皮层中发现的突触传递和同步性改变表明网络功能障碍。在这里，我们研究了 Cntnap2+/+ 和 Cntnap2-/- 成年小鼠晶须依赖性反应的神经底物。与对照组相比，Cntnap2-/小鼠在初级体感皮层 (S1) 内表现出局部超连接性，而 S1 和其他体感区域之间的连接性没有改变。该数据表明这些突变体中存在受损的体感处理。因此，Cntnap2-/-小鼠在纹理新物体识别测试（tNORT）中表现出胡须依赖性辨别力受损，并且在胡须刺激后S1内c-fos mRNA诱导增加。 S1 功能超连接可能是在 Cntnap2-/- 小鼠中观察到的异常胡须依赖性反应的基础，这表明 Cntnap2 小鼠是研究 ASD 特征的感觉异常的可靠模型。
Sensory abnormalities are a common feature in autism spectrum disorders (ASDs). Tactile responsiveness is altered in autistic individuals, with hypo-responsiveness being associated with the severity of ASD core symptoms. Similarly, sensory abnormalities have been described in mice lacking ASD-associated genes. Loss-offunction mutations in CNTNAP2 result in cortical dysplasia-focal epilepsy syndrome (CDFE) and autism. Likewise, Cntnap2-/- mice show epilepsy and deficits relevant with core symptoms of human ASDs, and are considered a reliable model to study ASDs. Altered synaptic transmission and synchronicity found in the cerebral cortex of Cntnap2-/- mice would suggest a network dysfunction. Here, we investigated the neural substrates of whisker-dependent responses in Cntnap2+/+ and Cntnap2-/- adult mice. When compared to controls, Cntnap2-/mice showed focal hyper-connectivity within the primary somatosensory cortex (S1), in the absence of altered connectivity between S1 and other somatosensory areas. This data suggests the presence of impaired somatosensory processing in these mutants. Accordingly, Cntnap2-/- mice displayed impaired whisker-dependent discrimination in the textured novel object recognition test (tNORT) and increased c-fos mRNA induction within S1 following whisker stimulation. S1 functional hyperconnectivity might underlie the aberrant whiskerdependent responses observed in Cntnap2-/- mice, indicating that Cntnap2 mice are a reliable model to investigate sensory abnormalities that characterize ASDs.