A Cross-Laboratory Investigation of Timing Endophenotypes in Mouse Behavior

Phenotyping behavioral and cognitive processes is a critical practice in mouse research and reliable phenotypic assessment is an essential component of building well-defined links between genes and behavioral/cognitive functions. The success of behavioral screens in neurobehavioral mouse genetics depends on the identification of reliable, reproducible, and high-throughput behavioral/cognitive measures from individual animals irrespective of the differences in opinions regarding how to tackle phenotyping in different behavioral domains. Furthermore, reliable behavioral assays must be resistant to inevitable environmental differences across laboratories since protocols can be replicated but not all the environmental conditions. Here we present a cross-laboratory study of interval timing behaviors in mice. Two classically used mouse inbred substrains, C57BL/6J and C57BL/6N, were studied over several days in home-cages containing automated testing apparatus. Remarkably, all timing measures in mouse performance showed a robust reproducibility across centers and even small differences between the two substrains were comparable across laboratories. Moreover, we have observed a consistent increase in error rate during the light phase of the light-dark cycle, which suggests that mouse performance during this phase is compromised by a possible sleep inertia-like effect. Overall, our study demonstrates that analysis of mouse timing behavior can lead to robust and reliable endophenotypes in mouse behavioral genetic studies.