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一种用于在亨廷顿舞蹈症大型非灵长类动物模型中测试认知能力的移动、高通量半自动系统。

A mobile, high-throughput semi-automated system for testing cognition in large non-primate animal models of Huntington disease.

作者信息

McBride Sebastian D, Perentos Nicholas, Morton A Jennifer

机构信息

Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

出版信息

J Neurosci Methods. 2016 May 30;265:25-33. doi: 10.1016/j.jneumeth.2015.08.025. Epub 2015 Aug 29.

DOI:10.1016/j.jneumeth.2015.08.025
PMID:26327320
Abstract

BACKGROUND

For reasons of cost and ethical concerns, models of neurodegenerative disorders such as Huntington disease (HD) are currently being developed in farm animals, as an alternative to non-human primates. Developing reliable methods of testing cognitive function is essential to determining the usefulness of such models. Nevertheless, cognitive testing of farm animal species presents a unique set of challenges. The primary aims of this study were to develop and validate a mobile operant system suitable for high throughput cognitive testing of sheep.

NEW METHOD

We designed a semi-automated testing system with the capability of presenting stimuli (visual, auditory) and reward at six spatial locations. Fourteen normal sheep were used to validate the system using a two-choice visual discrimination task. Four stages of training devised to acclimatise animals to the system are also presented.

RESULTS

All sheep progressed rapidly through the training stages, over eight sessions. All sheep learned the 2CVDT and performed at least one reversal stage. The mean number of trials the sheep took to reach criterion in the first acquisition learning was 13.9±1.5 and for the reversal learning was 19.1±1.8.

COMPARISON WITH EXISTING METHOD(S): This is the first mobile semi-automated operant system developed for testing cognitive function in sheep.

CONCLUSIONS

We have designed and validated an automated operant behavioural testing system suitable for high throughput cognitive testing in sheep and other medium-sized quadrupeds, such as pigs and dogs. Sheep performance in the two-choice visual discrimination task was very similar to that reported for non-human primates and strongly supports the use of farm animals as pre-clinical models for the study of neurodegenerative diseases.

摘要

背景

出于成本和伦理考量,目前正在农场动物中开发亨廷顿病(HD)等神经退行性疾病模型,以替代非人类灵长类动物。开发可靠的认知功能测试方法对于确定此类模型的实用性至关重要。然而,对农场动物物种进行认知测试面临一系列独特挑战。本研究的主要目的是开发并验证一种适用于绵羊高通量认知测试的移动操作性系统。

新方法

我们设计了一种半自动测试系统,能够在六个空间位置呈现刺激(视觉、听觉)和奖励。使用14只正常绵羊通过双选视觉辨别任务来验证该系统。还介绍了为使动物适应该系统而设计的四个训练阶段。

结果

所有绵羊在八个训练阶段中都进展迅速。所有绵羊都学会了双选视觉辨别任务并至少完成了一个反转阶段。绵羊在首次习得学习中达到标准所需的平均试验次数为13.9±1.5,在反转学习中为19.1±1.8。

与现有方法的比较

这是首个为测试绵羊认知功能而开发的移动半自动操作性系统。

结论

我们设计并验证了一种自动化操作性行为测试系统,适用于绵羊及其他中型四足动物(如猪和狗)的高通量认知测试。绵羊在双选视觉辨别任务中的表现与非人类灵长类动物的报道非常相似,有力地支持了将农场动物用作神经退行性疾病研究的临床前模型。

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