Reproducibility of behavioral phenotypes in mouse models - a short history with critical and practical notes

Abstract

Progress in pre-clinical research is built on reproducible findings, yet reproducibility has different dimensions and even meanings. Indeed, the terms reproducibility, repeatability, and replicability are often used interchangeably, although each has a distinct definition. Moreover, reproducibility can be discussed at the level of methods, analysis, results, or conclusions (1, 2). Despite these differences in definitions and dimensions, the main aim for an individual research group is the ability to develop new studies and hypotheses based on firm and reliable findings from previous experiments. In practice this wish is often difficult to accomplish. In this review, issues affecting reproducibility in the field of mouse behavioral phenotyping are discussed. Crisis in reproducibility. Over the last ten years, the "reproducibility crisis" has often appeared in the headlines of scientific journals (3-6). Several factors have been identified as the major causes for irreproducibility-including p-hacking, cherry-picking, low statistical power, publication bias, and hypothesizing after results are known (7). However, these issues mostly occur after the animal experiments are done. There are many more items to consider during the planning and running of an experiment-good experimental design includes considerations regarding randomization, blinding, details of housing, husbandry and animal care, the definition of the experimental unit, inclusion and exclusion criteria, and the choice of animal subjects (the source, health status, strain, sex and age of the animal), among others. (8-10). Guidelines and recommendations (e.g. ARRIVE, PREPARE) are available for addressing these factors (11, 12). However, despite the fact that the ARRIVE guidelines have existed for ten years and are

Role of Environment and Experimenter in Reproducibility of Behavioral Studies With Laboratory Mice

“…Therefore, planning checklists and culture of care (good communication) cannot be promoted enough (Smith, 2020;Robinson et al, 2021). Finally, we want emphasize experience and training for conducting behavioral experiments, because failure to consider essential factors affecting behavior of mice, interaction of mice and experimenters, and scoring behavior, may strongly influence the reproducibility, validity and reliability of the experiments (Blizard et al, 2007;Rodgers, 2007;Stanford, 2007;Schellinck et al, 2010;Voikar, 2020).…”

“…Measures of behavioral outcomes are therefore essential for characterizing the animal models of neurodegenerative and neuropsychiatric diseases. As a consequence, behavioral phenotyping of genetically modified mice has turned to be a commonly used approach in behavioral neuroscience and genetics over the last 25 years (Voikar, 2020).…”

Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives

“…Reproducibility of research, i.e., the ability of researchers to duplicate the results of a prior study (Goodman et al, 2016) is a growing concern in preclinical behavioral sciences (Steckler et al, 2015;Loken and Gelman, 2017;Voikar, 2020). An array of causative factors have been identified, including methodological discrepancies, variations in analysis and reporting structures, and differences in the conclusions between replicates of a study (Goodman et al, 2016).…”

Blueprints for measuring natural behavior

“…Yet, as shown by Wolfer et al. (2004) , enriching the environment does not hinder the reliability of the obtained results, while having significant advantages for animal welfare ( Balcombe, 2006 ; Bracke and Hopster, 2006 ; Loss et al., 2021 ; Voikar, 2020 ).…”