Berzhanskaya Julia, Phillips Marnie A, Gorin Alexis, Lai Chongxi, Shen Jing, Colonnese Matthew T
Department of Pharmacology and Physiology and Institute for Neuroscience.
Department of Electrical Engineering, School of Engineering and Applied Sciences, The George Washington University, Washington, DC 20052, USA.
Cereb Cortex. 2017 Feb 1;27(2):1386-1400. doi: 10.1093/cercor/bhv331.
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.
脆性X综合征（FXS）患儿存在注意力和觉醒缺陷。为了开始确定这些缺陷的神经学原因，我们研究了缺乏脆性X智力低下蛋白的幼年大鼠（FMR-KO），以观察与注意力和觉醒相关的皮质活动是否受到干扰。具体而言，我们研究了视觉皮层在激活状态和失活状态之间的转换，这两种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，出生后第三和第四周，运动期间的皮质活动以激活状态为主，有明显的18-52赫兹活动。然而，在安静休息期间，当野生型大鼠的活动以失活状态（3-9赫兹活动）为主时，FMR-KO大鼠的皮质异常地保持激活状态，导致休息期间高频功率增加，低频功率降低。放电率相关性显示，FMR-KO大鼠的同步性降低，特别是在快速放电中间神经元之间，这种情况在发育上先于皮质状态缺陷。我们的数据共同表明，抑制性连接的破坏损害了视觉皮层以行为适当的方式调节从激活状态退出的能力，这可能导致FXS患儿出现注意力和感觉处理障碍，因为未被注意的刺激更难降低皮质驱动。
