An automated maze task for assessing hippocampus-sensitive memory in mice.
An automated maze task for assessing hippocampus-sensitive memory in mice.
复制标题
DOI：
10.1016/j.bbr.2013.12.009
复制
发表时间：
2014-03-15
影响因子：
2.7
通讯作者：
Garner, Joseph P.
中科院分区：
文献类型：
--
作者：
Pioli, Elsa Y.;Gaskill, Brianna N.;Gilmour, Gary;Tricklebank, Mark D.;Dix, Sophie L.;Bannerman, David;Garner, Joseph P.
啮齿类动物的交替程序对海马的操纵高度敏感。然而，由于它们需要手动测试，它们的吞吐量低并且对动物有压力。开发了用于评估小鼠交替表现的自动迷宫。在海马损伤的小鼠中，交替表现受损。与海马功能障碍相关的记忆缺陷是许多神经退行性疾病和精神疾病的关键特征。离散试验奖励交替T-迷宫任务是高度敏感的海马功能障碍。正常小鼠具有自发性高水平的交替，而糖尿病损伤的小鼠则明显受损。然而，这是一个手工操作的任务，并且已经证明处理对行为反应具有关键影响，并且是劳动密集型的，因此不适合高通量研究。为了克服这个问题，设计了一个全自动迷宫。迷宫连接到小鼠的家笼，受试者通过跑过迷宫获得所有食物。在这项研究中，海马依赖奖励交替在自动迷宫进行了评估。根据交叉设计，在标准、手动运行、离散试验奖励交替范式和自动化范式中评估双侧海马损伤小鼠。在两个迷宫中发现了类似的对交替性能的鲁棒损伤效应，证实了自动迷宫对海马损伤的敏感性。此外，动物在自动迷宫中的表现不受其处理历史的影响，而在手动迷宫中的表现受先前测试历史的影响。通过具有更稳定的性能和通过减少人类接触，自动化迷宫可以提供减少外部实验变化的机会，从而增加实验室内和/或实验室之间的再现性。此外，自动化可能允许更大的实验通量，因此适用于在药物发现中评估认知功能。
Alternation procedures in rodents are highly sensitive to manipulations of the hippocampus. However as they require hand testing, they are low throughput and stressful for the animal. An automated maze was developed for assessing alternation performance in mice. Alternation performance was shown to be impaired in mice with lesions to the hippocampus. Memory deficits associated with hippocampal dysfunction are a key feature of a number of neurodegenerative and psychiatric disorders. The discrete-trial rewarded alternation T-maze task is highly sensitive to hippocampal dysfunction. Normal mice have spontaneously high levels of alternation, whereas hippocampal-lesioned mice are dramatically impaired. However, this is a hand-run task and handling has been shown to impact crucially on behavioural responses, as well as being labour-intensive and therefore unsuitable for high-throughput studies. To overcome this, a fully automated maze was designed. The maze was attached to the mouse's home cage and the subject earned all of its food by running through the maze. In this study the hippocampal dependence of rewarded alternation in the automated maze was assessed. Bilateral hippocampal-lesioned mice were assessed in the standard, hand-run, discrete-trial rewarded alternation paradigm and in the automated paradigm, according to a cross-over design. A similarly robust lesion effect on alternation performance was found in both mazes, confirming the sensitivity of the automated maze to hippocampal lesions. Moreover, the performance of the animals in the automated maze was not affected by their handling history whereas performance in the hand-run maze was affected by prior testing history. By having more stable performance and by decreasing human contact the automated maze may offer opportunities to reduce extraneous experimental variation and therefore increase the reproducibility within and/or between laboratories. Furthermore, automation potentially allows for greater experimental throughput and hence suitability for use in assessment of cognitive function in drug discovery.
登录
查看更多内容
影响因子：
48
作者：
Richter, S. Helene;Garner, Joseph P.;Wuerbel, Hanno
通讯作者：
Wuerbel, Hanno
影响因子：
2.9
作者：
Herremans, AHJ;Hijzen, TH;Slangen, JL
通讯作者：
Slangen, JL
影响因子：
3.5
作者：
Ainge, James A.;van der Meer, Matthijs A. A.;Wood, Emma R.
通讯作者：
Wood, Emma R.
影响因子：
25
作者：
Chapman, PF;White, GL;Hsiao, KK
通讯作者：
Hsiao, KK
影响因子：
2.7
作者：
Gerlai, R
通讯作者：
Gerlai, R