Selective increases in inter-individual variability in response to environmental enrichment in female mice

Abstract

One manifestation of individualization is a progressively differential response of individuals to the non-shared components of the same environment. Individualization has practical implications in the clinical setting, where subtle differences between patients are often decisive for the success of an intervention, yet there has been no suitable animal model to study its underlying biological mechanisms. Here we show that enriched environment (ENR) can serve as a model of brain individualization. We kept 40 isogenic female C57BL/6JRj mice for 3 months in ENR and compared these mice to an equally sized group of standard-housed control animals, looking at the effects on a wide range of phenotypes in terms of both means and variances. Although ENR influenced multiple parameters and restructured correlation patterns between them, it only increased differences among individuals in traits related to brain and behavior (adult hippocampal neurogenesis, motor cortex thickness, open field and object exploration), in agreement with the hypothesis of a specific activity-dependent development of brain individuality.

Early-life environmental enrichment generates persistent individualized behavior in mice

“…At the end of phase 1, body weight of ENR and ENR-STD mice was reduced compared to STD mice ( Fig. 1d; Table 1), which is consistent with the previously reported decrease of body weight by ENR 11,17 . However, within four weeks after returning ENR-STD mice to STD, their body weights increased to the levels observed in STD mice, while the long-term ENR group maintained lower body weights throughout phase 2 (Fig.…”

“…ENR enhances variance in adult hippocampal neurogenesis compared to STD mice, which we have previously related to the development of stable behavioral trajectories 9,11 . To analyze whether ENR has lasting consequences on individual rates of adult neurogenesis, we injected mice four weeks before the end of each phase with the thymidine analogues 5iododeoxyuridine (IdU; phase 1) and 5-chlorodeoxyuridine (CldU; phase 2) which can be separately detected by immunohistochemistry ( Fig.…”

“…A prime example of ENR-induced structural brain plasticity is the greater number of new neurons that are generated in the hippocampus of ENR-housed mice 17 . Our previous study has shown that, among a number of measures related to structural brain changes, adult hippocampal neurogenesis was the only phenotype, which, in ENR animals, showed enhanced variance in addition to increases in group means that have been reported in essentially all previous studies 11 . Furthermore, we have found that a substantial part of the variance in adult hippocampal neurogenesis (22 %) was explained by individualized behavioral trajectories that emerged during time in ENR 9 , linking individual experience with brain plasticity.…”

“…We next asked whether the stability of the emerged individual behaviors with time was dependent on continuous stimulation in ENR or whether behavioral patterns were also maintained after returning mice to STD cages as suggested by the lasting individualized hippocampal structures. We have recently shown that ENR-induced behavioral variability can be detected using open field and object exploration tests in a cross-sectional experimental design 11 . To investigate the long-lasting effects of ENR on behavioral variability, all mice…”

“…We have previously shown that environmental enrichment (ENR) promotes the development of behavioral variability between inbred C57BL6/JRj mice and proposed that ENR could be used as a tool to study brain individualization [9][10][11] . In those experiments, inter-individual differences among inbred mice emerged when they were housed in the same ENR cage, i.e.…”