Altered Neuronal Dynamics in the Striatum on the Behavior of Huntingtin Interacting Protein 14 (HIP14) Knockout Mice.
Altered Neuronal Dynamics in the Striatum on the Behavior of Huntingtin Interacting Protein 14 (HIP14) Knockout Mice.
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DOI：
10.3390/brainsci3041588
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发表时间：
2013-11-20
期刊：
影响因子：
3.3
通讯作者：
Rebec GV
中科院分区：
文献类型：
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作者：
Estrada-Sánchez AM;Barton SJ;Rebec GV
亨廷顿病(HD)是一种神经退行性疾病，由Huntingtin基因中CAG重复序列的扩大引起，它损害纹状体的信息处理，纹状体作为基底节的一部分，调节运动输出。越来越多的证据表明，亨廷顿蛋白相互作用蛋白14(HIP14)与HD神经病理有关。在这里，我们记录了HIP14基因敲除小鼠和野生型对照鼠在加型迷宫中自由航行时纹状体的局部场电位(LFP)。一旦进入迷宫的选择点，HIP14基因敲除的小鼠往往会继续直线运动，向左或向右转的频率明显低于野生型，这是运动缺乏灵活性的迹象，HD小鼠也会出现这种情况。纹状体LFP活性预测到了这种差异。在野生型中，与进入选择点相关的功率谱密度模式与进入选择点前的模式显著不同，特别是在低频(≤13赫兹)，而HIP14基因敲除在进入选择点时没有显示出LFP活性的变化。纹状体活动缺乏变化可能解释了正迷宫中的转折缺陷。我们的结果表明，HIP14在纹状体神经元活动的异常行为调节中起关键作用，这些活动是导致运动不灵活的基础，包括HD的运动体征。
Huntington’s disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, impairs information processing in the striatum, which, as part of the basal ganglia, modulates motor output. Growing evidence suggests that huntingtin interacting protein 14 (HIP14) contributes to HD neuropathology. Here, we recorded local field potentials (LFPs) in the striatum as HIP14 knockout mice and wild-type controls freely navigated a plus-shaped maze. Upon entering the choice point of the maze, HIP14 knockouts tend to continue in a straight line, turning left or right significantly less often than wild-types, a sign of motor inflexibility that also occurs in HD mice. Striatal LFP activity anticipates this difference. In wild-types, the power spectral density pattern associated with entry into the choice point differs significantly from the pattern immediately before entry, especially at low frequencies (≤13 Hz), whereas HIP14 knockouts show no change in LFP activity as they enter the choice point. The lack of change in striatal activity may explain the turning deficit in the plus maze. Our results suggest that HIP14 plays a critical role in the aberrant behavioral modulation of striatal neuronal activity underlying motor inflexibility, including the motor signs of HD.