Department of Psychiatry, 3811 O'Hara Street, BST W1643, University of Pittsburgh, Pittsburgh, PA 15213, USA.
J Neurosci Methods. 2011 Apr 15;197(1):21-31. doi: 10.1016/j.jneumeth.2011.01.019. Epub 2011 Jan 26.
Defining anxiety- and depressive-like states in mice (emotionality) is best characterized by the use of complementary tests, leading sometimes to puzzling discrepancies and lack of correlation between similar paradigms. To address this issue, we hypothesized that integrating measures along the same behavioral dimensions in different tests would reduce the intrinsic variability of single tests and provide a robust characterization of the underlying "emotionality" of individual mouse, similarly as mood and related syndromes are defined in humans through various related symptoms over time. We describe the use of simple mathematical and integrative tools to help phenotype animals across related behavioral tests (syndrome diagnosis) and experiments (meta-analysis). We applied z-normalization across complementary measures of emotionality in different behavioral tests after unpredictable chronic mild stress (UCMS) or prolonged corticosterone exposure - two approaches to induce anxious-/depressive-like states in mice. Combining z-normalized test values, lowered the variance of emotionality measurement, enhanced the reliability of behavioral phenotyping, and increased analytical opportunities. Comparing integrated emotionality scores across studies revealed a robust sexual dimorphism in the vulnerability to develop high emotionality, manifested as higher UCMS-induced emotionality z-scores, but lower corticosterone-induced scores in females compared to males. Interestingly, the distribution of individual z-scores revealed a pattern of increased baseline emotionality in female mice, reminiscent of what is observed in humans. Together, we show that the z-scoring method yields robust measures of emotionality across complementary tests for individual mice and experimental groups, hence facilitating the comparison across studies and refining the translational applicability of these models.
定义小鼠的焦虑和抑郁样状态（情绪）最好通过使用互补测试来进行，这有时会导致类似范式之间令人困惑的差异和缺乏相关性。为了解决这个问题，我们假设在不同测试中沿着相同的行为维度整合测量将减少单个测试的固有变异性，并为个体小鼠的潜在“情绪”提供稳健的特征描述，就像通过随着时间的推移在人类中通过各种相关症状来定义情绪和相关综合征一样。我们描述了使用简单的数学和综合工具来帮助在相关行为测试（综合征诊断）和实验（荟萃分析）中对动物进行表型分析。我们在不同行为测试中对不可预测的慢性轻度应激（UCMS）或长期皮质酮暴露后进行情绪的互补测量进行 z 归一化-这两种方法可诱导小鼠出现焦虑/抑郁样状态。组合 z 归一化测试值降低了情绪测量的方差，增强了行为表型分析的可靠性，并增加了分析机会。比较跨研究的综合情绪评分揭示了在易感性方面存在显著的性别二态性，表现为 UCMS 诱导的情绪 z 评分较高，但与雄性相比，雌性的皮质酮诱导评分较低。有趣的是，个体 z 评分的分布显示出雌性小鼠基础情绪增加的模式，这让人联想到在人类中观察到的模式。总之，我们表明 z 评分方法可在个体小鼠和实验组的互补测试中产生稳健的情绪测量值，从而促进跨研究比较并提高这些模型的转化适用性。
