Dendritic Spines in Early Postnatal Fragile X Mice Are Insensitive to Novel Sensory Experience
Dendritic Spines in Early Postnatal Fragile X Mice Are Insensitive to Novel Sensory Experience
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DOI：
10.1523/jneurosci.1734-18.2018
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发表时间：
2019-01-16
影响因子：
5.3
通讯作者：
Portera-Cailliau, Carlos
中科院分区：
文献类型：
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作者：
Arroyo, Erica D.;Fiole, Daniel;Portera-Cailliau, Carlos
自闭症谱系障碍通常与非典型的感觉加工和感觉过敏有关，这可能导致不良适应行为，如触觉防御。自闭症谱系障碍的这种感觉变化可能是由于早期大脑发育过程中依赖经验的神经回路成熟的中断造成的。在这里，我们检验了一种假设，即脆性X综合征(FXS)的初级躯体感觉皮质(S1)神经元的突触结构在发育过程中不受新的感觉信息的调节。FXS是自闭症的常见遗传原因。我们用双光子显微镜对FXS模型雄性和雌性WT和Fmr1KO小鼠S1层2/3层锥体神经元的树突棘和轴突进行了成像。我们发现，在出生后第二周，短暂(过夜)暴露于显著增强感觉输入的环境中，会导致WT鼠的脊柱密度显著增加，但在Fmr1KO鼠中并非如此。相反，在这两种类型的小鼠中，轴突“沿途”的轴突动力学不受这种新的感觉体验的影响。我们推测，Fmr1 KO小鼠在感觉信息处理首次在S1皮质上线时，无法调节突触后动力学以响应增加的感觉输入，可能在FXS的感觉处理改变中发挥作用。
Autism spectrum disorders are often associated with atypical sensory processing and sensory hypersensitivity, which can lead to maladaptive behaviors, such as tactile defensiveness. Such altered sensory perception in autism spectrum disorders could arise from disruptions in experience-dependent maturation of circuits during early brain development. Here, we tested the hypothesis that synaptic structures of primary somatosensory cortex (S1) neurons in Fragile X syndrome (FXS), which is a common inherited cause of autism, are not modulated by novel sensory information during development. We used chronic in vivo two-photon microscopy to image dendritic spines and axon "en passant" boutons of layer 2/3 pyramidal neurons in S1 of male and female WT and Fmr1 KO mice, a model of FXS. We found that a brief (overnight) exposure to dramatically enhance sensory inputs in the second postnatal week led to a significant increase in spine density inWTmice, but not in Fmr1 KO mice. In contrast, axon "en passant" boutons dynamics were impervious to this novel sensory experience in mice of both genotypes. We surmise that the inability of Fmr1 KO mice to modulate postsynaptic dynamics in response to increased sensory input, at a time when sensory information processing first comes online in S1 cortex, could play a role in altered sensory processing in FXS.