Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom; Department of Neurology, Klinikum recht der Isar, Technical University Munich, Munich, Germany.
J Neurosci Methods. 2021 Mar 1;351:109009. doi: 10.1016/j.jneumeth.2020.109009. Epub 2020 Dec 16.
Cognitive impairment is a distinguishing feature of many neurodegenerative diseases. The intra-dimensional (ID) extra-dimensional (ED) attentional set shift task is part of a clinical battery of tests used to evaluate executive function in Huntington's and Alzheimer's disease patients. The IDED task, however, has not translated well to pre-clinical rodent models of neurological disease.
The ability to perform executive tasks coupled with a long lifespan makes sheep (Ovis aries) an ideal species for modelling cognitive decline in progressive neurodegenerative conditions. We describe the methodology for testing the performance of sheep in the IDED task using a semi-automated system in which visual stimuli are presented as coloured letters on computer screens.
During each stage of IDED testing, all sheep (n = 12) learned successfully to discriminate between different colours and letters. Sheep were quick to learn the rules of acquisition at each stage. They required significantly more trials to reach criterion (p < 0.05) and made more errors (p < 0.05) following stimulus reversal, with the exception of the ED shift (p > 0.05).
COMPARISON WITH EXISTING METHOD(S): Previous research shows that sheep can perform IDED set shifting in a walk-through maze using solid objects with two changeable dimensions (colour and shape) as the stimuli. Presenting the stimuli on computer screens provides better validity, greater task flexibility and higher throughput than the walk-through maze.
All sheep completed each stage of the task, with a range of abilities expected in an outbred population. The IDED task described is ideally suited as a quantifiable and clinically translatable measure of executive function in sheep.
认知障碍是许多神经退行性疾病的一个显著特征。内维度（ID）外维度（ED）注意定势转移任务是用于评估亨廷顿氏病和阿尔茨海默氏病患者执行功能的临床测试组合的一部分。然而，IDED 任务并没有很好地转化为神经疾病的临床前啮齿动物模型。
执行任务的能力加上较长的寿命，使绵羊（Ovis aries）成为模拟进行性神经退行性疾病中认知能力下降的理想物种。我们描述了使用半自动系统测试绵羊在 IDED 任务中的表现的方法，其中视觉刺激以彩色字母的形式呈现在计算机屏幕上。
在 IDED 测试的每个阶段，所有绵羊（n = 12）都成功地学会了区分不同的颜色和字母。绵羊很快就学会了每个阶段的获取规则。与刺激反转后相比，它们需要更多的试验才能达到标准（p < 0.05），并且犯的错误更多（p < 0.05），除了 ED 转移（p > 0.05）。
以前的研究表明，绵羊可以在使用具有两个可变性尺寸（颜色和形状）的实心物体的走迷宫中执行 IDED 定势转移作为刺激。在计算机屏幕上呈现刺激比走迷宫提供了更好的有效性、更大的任务灵活性和更高的吞吐量。
所有绵羊都完成了任务的每个阶段，预计在杂种群体中会有一系列的能力。所描述的 IDED 任务非常适合作为绵羊执行功能的可量化和临床可转化的衡量标准。
