Disrupted Cortical State Regulation in a Rat Model of Fragile X Syndrome
Disrupted Cortical State Regulation in a Rat Model of Fragile X Syndrome
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DOI：
10.1093/cercor/bhv331
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发表时间：
2017-02-01
期刊：
影响因子：
3.7
通讯作者：
Colonnese, Matthew T.
中科院分区：
文献类型：
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作者：
Berzhanskaya, Julia;Phillips, Marnie A.;Colonnese, Matthew T.
患有脆性X综合征（FXS）的儿童存在注意力和唤醒缺陷。为了开始确定这些缺陷的神经原因，我们检查了缺乏脆性X智力低下蛋白（FMR-KO）的幼年大鼠与注意力和唤醒相关的皮质活动的中断。具体来说，我们研究了视觉皮层在激活和失活状态之间的切换，这些状态通常分别发生在运动和安静休息期间。在野生型和FMR-KO大鼠中，在出生后第三和第四周，运动期间的皮质活动主要由具有突出的18-52 Hz活动的激活状态主导。然而，在安静休息期间，当野生型大鼠的活动由失活状态（3-9 Hz活动）主导时，FMR-KO大鼠皮质异常地保持激活，导致休息期间高频功率增加和低频功率减少。放电率的相关性显示减少FMR-KO大鼠的同步，特别是快速尖峰的中间神经元，发育之前皮质状态的缺陷。总之，我们的数据表明，中断的抑制连接损害视觉皮层的能力，以适当的行为方式调节退出激活状态，可能有助于干扰注意力和感觉处理观察FXS儿童，使其更难以减少皮质驱动无人看管的刺激。
Children with Fragile X syndrome (FXS) have deficits of attention and arousal. To begin to identify the neural causes of these deficits, we examined juvenile rats lacking the Fragile X mental retardation protein (FMR-KO) for disruption of cortical activity related to attention and arousal. Specifically, we examined the switching of visual cortex between activated and inactivated states that normally occurs during movement and quiet rest, respectively. In both wild-type and FMR-KO rats, during the third and fourth postnatal weeks cortical activity during periods of movement was dominated by an activated state with prominent 18-52 Hz activity. However, during quiet rest, when activity in wild-type rats became dominated by the inactivated state (3-9 Hz activity), FMR-KO rat cortex abnormally remained activated, resulting in increased high-frequency and reduced low-frequency power during rest. Firing rate correlations revealed reduced synchronization in FMR-KO rats, particularly between fast-spiking interneurons, that developmentally precede cortical state defects. Together our data suggest that disrupted inhibitory connectivity impairs the ability of visual cortex to regulate exit from the activated state in a behaviorally appropriate manner, potentially contributing to disrupted attention and sensory processing observed in children with FXS by making it more difficult to decrease cortical drive by unattended stimuli.