Boutet Isabelle, Collin Charles A, MacLeod Lindsey S, Messier Claude, Holahan Matthew R, Berry-Kravis Elizabeth, Gandhi Reno M, Kogan Cary S
School of Psychology, University of Ottawa, Ottawa, ON, Canada.
Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
Front Mol Neurosci. 2018 Mar 28;11:99. doi: 10.3389/fnmol.2018.00099. eCollection 2018.
To generate meaningful information, translational research must employ paradigms that allow extrapolation from animal models to humans. However, few studies have evaluated translational paradigms on the basis of defined validation criteria. We outline three criteria for validating translational paradigms. We then evaluate the Hebb-Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as model disease. We focused on this paradigm because it allows direct comparison of humans and animals on tasks that are behaviorally equivalent (criterion #1) and because it measures spatial information processing, a cognitive domain for which FXS individuals and mice show impairments as compared to controls (criterion #2). We directly compared the performance of affected humans and mice across different experimental conditions and measures of behavior to identify which conditions produce comparable patterns of results in both species. Species differences were negligible for Mazes 2, 4, and 5 irrespective of the presence of visual cues, suggesting that these mazes could be used to measure spatial learning in both species. With regards to performance on the first trial, which reflects visuo-spatial problem solving, Mazes 5 and 9 without visual cues produced the most consistent results. We conclude that the Hebb-Williams mazes paradigm has the potential to be utilized in translational research to measure comparable cognitive functions in FXS humans and animals (criterion #3).
为了生成有意义的信息，转化研究必须采用能够从动物模型外推至人类的范式。然而，很少有研究基于明确的验证标准对转化范式进行评估。我们概述了验证转化范式的三个标准。然后，我们以脆性X综合征（FXS）作为模型疾病，根据这些标准对赫布-威廉姆斯迷宫范式（赫布和威廉姆斯，1946年；拉宾诺维奇和罗斯沃尔德，1951年）进行评估。我们关注这个范式，是因为它能让人类和动物在行为上等效的任务上进行直接比较（标准#1），还因为它测量空间信息处理，这是一个认知领域，与对照组相比，FXS个体和小鼠在该领域表现出损伤（标准#2）。我们直接比较了受影响的人类和小鼠在不同实验条件和行为测量下的表现，以确定哪些条件在两个物种中产生可比的结果模式。无论是否存在视觉线索，迷宫2、4和5的物种差异都可以忽略不计，这表明这些迷宫可用于测量两个物种的空间学习。关于反映视觉空间问题解决能力的首次试验表现，没有视觉线索的迷宫5和9产生了最一致的结果。我们得出结论，赫布-威廉姆斯迷宫范式有潜力用于转化研究，以测量FXS人类和动物中可比的认知功能（标准#3）。
