Changes in striatal procedural memory coding correlate with learning deficits in a mouse model of Huntington disease
Changes in striatal procedural memory coding correlate with learning deficits in a mouse model of Huntington disease
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DOI：
10.1073/pnas.1016190108
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发表时间：
2011-05-31
影响因子：
11.1
通讯作者：
Cho, Yoon H.
中科院分区：
文献类型：
--
作者：
Cayzac, Sebastien;Delcasso, Sebastien;Cho, Yoon H.
在遗传性神经退行性亨廷顿病(HD)中，运动障碍之前的早期认知障碍被认为是由于变性前纹状体和皮质的功能障碍造成的。为了验证这一假设，我们检测了运动症状前期的R6/1转基因小鼠在进行程序性学习任务时，纹状体和皮质中单个细胞的放电特性和局部场活动，这一任务的表现通常取决于纹状体和基底节的完整性。在这里，我们报告说，与WT小鼠相比，R6/1小鼠在编码这项任务时脆弱的纹状体投射细胞，而不是局部中间神经元的招募显著减少，与程序性学习的严重缺陷有关。此外，这些小鼠的纹状体和皮质在高频下都表现出独特的振荡。这些数据提供了关于HD突变对早期HD认知能力产生影响的皮质纹状体通路中体内细胞过程的关键信息。
In hereditary neurodegenerative Huntington disease (HD), early cognitive impairments before motor deficits have been hypothesized to result from dysfunction in the striatum and cortex before degeneration. To test this hypothesis, we examined the firing properties of single cells and local field activity in the striatum and cortex of pre-motor-symptomatic R6/1 transgenic mice while they were engaged in a procedural learning task, the performance on which typically depends on the integrity of striatum and basal ganglia. Here, we report that a dramatically diminished recruitment of the vulnerable striatal projection cells, but not local interneurons, of R6/1 mice in coding for the task, compared with WT littermates, is associated with severe deficits in procedural learning. In addition, both the striatum and cortex in these mice showed a unique oscillation at high.-frequency. These data provide crucial information on the in vivo cellular processes in the corticostriatal pathway through which the HD mutation exerts its effects on cognitive abilities in early HD.