When numbers become individuals: Improving the quality of behavioral animal experiments by mapping and incorporating inter-individuality in mice.

Abstract

In preclinical experimental animal research, inter-individual variability in phenotypic response is a major source of within-group variability that may negatively affect the power of animal experiments and the reproducibility of their outcomes. Individual differences however are often not actively accounted for in the design of animal experiments. The importance of accounting for this variability has become especially acknowledged in animal models that study the underlying mechanisms and/or treatment of psychiatric diseases. In humans, the susceptibility to develop psychopathologies and the response to treatment is known to vary greatly between patients. Incorporating this variation in animal models may not only make these models more representative, but could also improve our understanding of the underlying mechanisms that are involved in this differential susceptibility. In the present thesis we focused on inter-individual variability in habituation of anxiety responses in mice. The overarching aim of the studies was twofold: To improve our understanding of this variability by mapping its expression on a behavioral and physiological level in three commonly used mouse inbred strains. And: to explore whether systematic incorporation of such inter-individual variability in the analysis and design of our experiments would affect the quality of our results. By applying a multidimensional, individual-based analysis approach we identified two behavioral response types which were displayed by individuals of all three inbred strains. We subsequently demonstrated how controlling for this type of variability may affect the quality of experimental results, and may facilitate a more comprehensive understanding of inter-individuality in anxiety responses in mice.