The individuality paradigm: Automated longitudinal activity tracking of large cohorts of genetically identical mice in an enriched environment

Personalized medicine intensifies interest in experimental paradigms that delineate sources of phenotypic variation. The paradigm of environmental enrichment allows for comparisons among differently housed labo-ratory rodents to unravel environmental effects on brain plasticity and related phenotypes. We have developed a new longitudinal variant of this paradigm, which allows to investigate the emergence of individuality, the divergence of individual behavioral trajectories under a constant genetic background and in a shared environ-ment. We here describe this novel method, the Individuality Paradigm, which allows to investigate mecha-nisms that drive individuality. Various aspects of individual activity are tracked over time to identify the contribution of the non-shared environment, that is the extent to which the experience of an environment differs between individual members of a population. We describe the design of this paradigm in detail, lay out its scientific potential beyond the published studies and discuss how it differs from other approaches to study in-dividuality. The custom-built cage system, commercially marketed as ColonyRack, allows mice to roam freely between 70 cages through connector tubes equipped with ring antennas that detect each animal's ID from an RFID transponder implanted in the animal's neck. The system has a total floor area of 2.74 m2 and its spatial resolution corresponds to the size of the individual cages. Spatiotemporally resolved antenna contacts yield longitudinal measures of individual behavior, including the powerful measure of roaming entropy (RE). The Individuality Paradigm provides a rodent model of the making of individuality and the impact of the 'non-shared' environment on life-course development.

Automated summary

Personalized medicine has sparked great interest in understanding the sources of phenotypic variation, especially the impact of the environment on brain plasticity and phenotypes. This article introduces a new longitudinal paradigm, the Individuality Paradigm, which allows for the investigation of individual differences and the divergence of individual behavioral trajectories under a constant genetic background and shared environment. By tracking various aspects of individual activity over time, the contribution of the non-shared environment can be identified. This paradigm offers a rodent model to study individual differences and the influence of the "non-shared" environment on life-course development.