Sensory hypo-excitability in a rat model of fetal development in Fragile X Syndrome.
Sensory hypo-excitability in a rat model of fetal development in Fragile X Syndrome.
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DOI：
10.1038/srep30769
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发表时间：
2016-07-28
影响因子：
4.6
通讯作者：
Colonnese MT
中科院分区：
文献类型：
--
作者：
Berzhanskaya J;Phillips MA;Shen J;Colonnese MT
脆性 X 综合征 (FXS) 的特点是感觉超敏，动物模型表明神经元过度兴奋导致了这种表型。为了了解 FXS 中感觉功能障碍是如何发展的，我们使用大鼠模型 (FMR-KO) 来量化从睁眼之前的反应开始到人类青少年的年龄相当的皮层视觉反应的成熟程度。睁眼前的视觉反应不是过度兴奋，而是降低了尖峰率，并且缺乏早期伽马振荡，这是该年龄正常丘脑功能的标志。尽管早期兴奋性低下，但 FMR-KO 大鼠的视觉反应发育轨迹正常，并且在与野生型大鼠相同的年龄（睁眼前两天）表现出预期的视觉诱发爆发消失。在后来的年龄，在产后第三周和第四周，出现了轻度过度兴奋的迹象。这些包括视觉诱发的规则尖峰、假定的兴奋性神经元的放电增加，以及快速尖峰、假定的抑制性神经元的放电减少。我们的结果表明，FMR-KO 大鼠的早期网络变化发生在与人类胎儿相当的年龄，并且对兴奋性的影响与成人中发现的相反。这表明识别和治疗应尽早开始，并以适合年龄的方式进行调整。
Fragile X syndrome (FXS) is characterized by sensory hyper-sensitivity, and animal models suggest that neuronal hyper-excitability contributes to this phenotype. To understand how sensory dysfunction develops in FXS, we used the rat model (FMR-KO) to quantify the maturation of cortical visual responses from the onset of responsiveness prior to eye-opening, through age equivalents of human juveniles. Rather than hyper-excitability, visual responses before eye-opening had reduced spike rates and an absence of early gamma oscillations, a marker for normal thalamic function at this age. Despite early hypo-excitability, the developmental trajectory of visual responses in FMR-KO rats was normal, and showed the expected loss of visually evoked bursting at the same age as wild-type, two days before eye-opening. At later ages, during the third and fourth post-natal weeks, signs of mild hyper-excitability emerged. These included an increase in the visually-evoked firing of regular spiking, presumptive excitatory, neurons, and a reduced firing of fast-spiking, presumptive inhibitory, neurons. Our results show that early network changes in the FMR-KO rat arise at ages equivalent to fetal humans and have consequences for excitability that are opposite those found in adults. This suggests identification and treatment should begin early, and be tailored in an age-appropriate manner.