Fragile X syndrome (FXS) is the most prevalent inherited cause of autism and is accompanied by behavioral and sensory deficits. Errors in the wiring of the brain during early development likely contribute to these deficits, but the underlying mechanisms are unclear. Spontaneous activity patterns, which are required for fine-tuning neuronal networks before the senses become active, are perturbed in rodent models of FXS. Here, we investigated spontaneous network activity patterns in the developing visual cortex of the Fmr1 knockout mouse using in vivo calcium imaging during the second postnatal week, before eye opening. We found that while the frequency, mean amplitude and duration of spontaneous network events were unchanged in the knockout mouse, pair-wise correlations between neurons were increased compared to wild type littermate controls. Further analysis revealed that interneuronal correlations were not generally increased, rather that low-synchronization events occurred relatively less frequently than high-synchronization events. Low-, but not high-, synchronization events have been associated with retinal inputs previously. Since we found that spontaneous retinal waves were normal in the knockout, our results suggest that peripherally driven activity is underrepresented in the Fmr1 KO visual cortex. Therefore, we propose that central gating of retinal inputs may be affected in FXS and that peripherally and centrally driven activity patterns are already unbalanced before eye opening in this disorder.

中文翻译：

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自发活动模式在Fmr1基因敲除小鼠的发育中的视觉皮层中更改。

脆性X综合征（FXS）是自闭症最普遍的遗传原因，并伴有行为和感觉缺陷。早期发育过程中大脑连线的错误可能是造成这些缺陷的原因，但其潜在机制尚不清楚。FXS啮齿动物模型会扰动自发活动模式，这是在感觉变得活跃之前微调神经网络所需的。在这里，我们调查了出生后第二周，在睁眼之前使用体内钙成像技术，研究了Fmr1基因敲除小鼠的发育中视觉皮层的自发网络活动模式。我们发现，虽然基因敲除小鼠的自发网络事件的频率，平均振幅和持续时间没有变化，但与野生型同窝对照相比，神经元之间的成对相关性却增加了。进一步的分析表明，神经元间的相关性通常没有增加，相反，低同步事件的发生频率比高同步事件的发生频率相对较低。低但不是高同步事件以前已与视网膜输入相关联。由于我们发现基因敲除的自发性视网膜波正常，因此我们的结果表明，在Fmr1 KO视觉皮层中外周驱动的活性不足。因此，我们建议在FXS中可能会影响视网膜输入的中央门控，并且在这种疾病中，在睁眼之前，周围和中央驱动的活动模式已经不平衡。相反，与高同步事件相比，低同步事件发生的频率相对较低。低但不是高同步事件以前已与视网膜输入相关联。由于我们发现基因敲除的自发性视网膜波正常，因此我们的结果表明，在Fmr1 KO视觉皮层中外周驱动的活性不足。因此，我们建议在FXS中可能会影响视网膜输入的中央门控，并且在这种疾病中，在睁眼之前，周围和中央驱动的活动模式已经不平衡。相反，与高同步事件相比，低同步事件发生的频率相对较低。低但不是高同步事件以前已与视网膜输入相关联。由于我们发现基因敲除的自发性视网膜波正常，因此我们的结果表明，在Fmr1 KO视觉皮层中外周驱动的活性不足。因此，我们建议在FXS中可能会影响视网膜输入的中央门控，并且在这种疾病中，在睁眼之前，周围和中央驱动的活动模式已经不平衡。我们的结果表明，在Fmr1 KO视觉皮层中外周驱动的活性不足。因此，我们建议在FXS中可能会影响视网膜输入的中央门控，并且在这种疾病中，在睁眼之前，周围和中央驱动的活动模式已经不平衡。我们的结果表明，在Fmr1 KO视觉皮层中外周驱动的活性不足。因此，我们建议在FXS中可能会影响视网膜输入的中央门控，并且在这种疾病中，在睁眼之前，周围和中央驱动的活动模式已经不平衡。