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首页> 美国卫生研究院文献>Frontiers in Behavioral Neuroscience >Impaired Performance of the Q175 Mouse Model of Huntington’s Disease in the Touch Screen Paired Associates Learning Task
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Impaired Performance of the Q175 Mouse Model of Huntington’s Disease in the Touch Screen Paired Associates Learning Task

机译：触摸屏配对员工学习任务中亨廷顿氏病Q175小鼠模型的性能受损

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Cognitive disturbances often predate characteristic motor dysfunction in individuals with Huntington’s disease (HD) and place an increasing burden on the HD patients and caregivers with the progression of the disorder. Therefore, application of maximally translational cognitive tests to animal models of HD is imperative for the development of treatments that could alleviate cognitive decline in human patients. Here, we examined the performance of the Q175 mouse knock-in model of HD in the touch screen version of the paired associates learning (PAL) task. We found that 10–11-month-old heterozygous Q175 mice had severely attenuated learning curve in the PAL task, which was conceptually similar to previously documented impaired performance of individuals with HD in the PAL task of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Besides high rate of errors in PAL task, Q175 mice exhibited considerably lower responding rate than age-matched wild-type (WT) animals. Our examination of effortful operant responding during fixed ratio (FR) and progressive ratio (PR) reinforcement schedules in a separate cohort of similar age confirmed slower and unselective performance of mutant animals, as observed during PAL task, but suggested that motivation to work for nutritional reward in the touch screen setting was similar in Q175 and WT mice. We also demonstrated that pronounced sensorimotor disturbances in Q175 mice can be detected at early touch screen testing stages, (e.g., during “Punish Incorrect” phase of operant pretraining), so we propose that shorter test routines may be utilised for more expedient studies of treatments aimed at the rescue of HD-related phenotype.
机译：认知障碍通常在亨廷顿舞蹈病（HD）患者出现特征性运动功能障碍之前出现，并随着疾病的发展给HD患者和护理人员增加负担。因此，将最大转化认知测试应用于HD动物模型对于开发可减轻人类患者认知能力下降的治疗方法势在必行。在这里，我们研究了在配对员工学习（PAL）任务的触摸屏版本中，HD Q175鼠标敲入模型的性能。我们发现10-11个月大的Q175杂合小鼠在PAL任务中的学习曲线严重减弱，这在概念上类似于先前在剑桥神经心理测试自动电池（CANTAB）的PAL任务中记录的HD患者的表现受损。 。除了PAL任务中的错误率很高外，Q175小鼠的反应率也比年龄匹配的野生型（WT）动物低得多。如在PAL任务中观察到的，我们对固定比率（FR）和渐进比率（PR）强化时间表中努力的操作员响应的检查在一个类似年龄的单独队列中进行了研究，证实了突变动物的运动较慢和非选择性，但建议其从事营养工作的动机Q175和WT小鼠在触摸屏上的奖励相似。我们还证明了在早期触摸屏测试阶段（例如，在操作性预训练的“惩罚不正确”阶段）可以检测到Q175小鼠明显的感觉运动障碍，因此我们建议可以将较短的测试程序用于更便捷的治疗研究旨在挽救与HD相关的表型。

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