Integrated behavioral z-scoring increases the sensitivity and reliability of behavioral phenotyping in mice: relevance to emotionality and sex.
Integrated behavioral z-scoring increases the sensitivity and reliability of behavioral phenotyping in mice: relevance to emotionality and sex.
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综合行为 z 评分提高了小鼠行为表型的敏感性和可靠性：与情绪和性的相关性。
DOI：
10.1016/j.jneumeth.2011.01.019
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发表时间：
2011-04-15
影响因子：
3
通讯作者：
Sibille, Etienne
中科院分区：
文献类型：
--
作者：
Guilloux, Jean-Philippe;Seney, Marianne;Edgar, Nicole;Sibille, Etienne
在小鼠中定义焦虑和抑郁样状态（“情绪性”）最好通过使用补充测试来表征，有时会导致令人困惑的差异和相似范式之间缺乏相关性。为了解决这个问题，我们假设，整合措施沿着相同的行为维度在不同的测试将减少单一测试的内在变异性，并提供了一个强大的表征的潜在的“情绪”的个别小鼠，类似的情绪和相关的综合征定义在人类中通过各种相关的症状随着时间的推移。我们描述了使用简单的数学和综合工具，以帮助表型动物在相关的行为测试（综合征诊断）和实验（荟萃分析）。我们在不可预测的慢性轻度应激（UCMS）或长时间皮质酮暴露后的不同行为测试中对情绪性的补充测量进行了z归一化-这是诱导小鼠焦虑/抑郁样状态的两种方法。结合z归一化的测试值，降低了情绪测量的方差，增强了行为表型的可靠性，并增加了分析的机会。比较综合情绪分数在研究中发现了一个强大的性二态性的脆弱性发展高情绪，表现为较高的UCMS诱导的情绪Z分数，但较低的皮质酮诱导的分数在女性相比，男性。有趣的是，个体z分数的分布揭示了雌性小鼠中基线情绪增加的模式，让人想起在人类中观察到的情况。总之，我们表明，z评分方法在单个小鼠和实验组的互补测试中产生了强大的情感测量，从而促进了研究之间的比较，并改进了这些模型的翻译适用性。
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.
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