Early-life environmental enrichment generates persistent individualized behavior in mice

Abstract

Individuals differ in their response to environmental stimuli, but the stability of individualized behaviors and their associated changes in brain plasticity are poorly understood. We developed a novel model of enriched environment to longitudinally monitor 40 inbred mice exploring 35 connected cages over periods of three to six months. We show that behavioral individuality that emerged during the first three months of environmental enrichment persisted when mice were withdrawn from the enriched environment for three additional months. Behavioral trajectories were associated with stable inter-individual differences in adult hippocampal neurogenesis and persistent epigenetic effects on neuronal plasticity genes in the hippocampus. Using genome-wide DNA methylation sequencing, we show that one third of the DNA methylation changes were maintained after withdrawal from the enriched environment. Our results suggest that, even under the most constraint conditions controlling genes and environment, early-life experiences result in lasting individualized changes in behavior and brain plasticity.

Estimating Nonlinear Selection on Behavioral Reaction Norms

“…Bierbach, Laskowski, and Wolf (2017), for example, found that personality emerged in activity level among clonal fish raised in highly controlled environmental conditions, likely as a result of developmental noise. Similar findings have been obtained for clonal mice, where individuality in behavior can result from subtle differences in neurobiological and epigenetic responses toward standardized early rearing environments (Zocher et al 2020). Processes such as mutation-selection balance also remain plausible explanations for the maintenance of non-adaptive behavioral variation even in the presence of consistent stabilizing selection (Zhang and Hill 2005), particularly for complex traits with large mutational target sizes caused by highly polygenic and pleiotropic developmental pathways (Houle 1998;Boyle, Li, and Pritchard 2017).…”

Effects of enriched environment on micturition activity in freely moving C57BL/6J mice

“…It was suggested that the effect of enrichment on micturition activity may persist even after withdrawal from the EE. Previous studies have shown that an EE led to changes in cerebral cortex weight, 47 cortical acetylcholinesterase activity, 47 and object exploration, 48 which persisted for 3 to 12 weeks after withdrawal from the EE. Although these previous reports were related to higher brain function, we found that the effect of an EE can also be seen in brain stem functions, such as micturition.…”

De novoDNA methylation controls neuronal maturation during adult hippocampal neurogenesis

“…Environmental enrichment (ENR) is a strong pro-neurogenic stimulus that predominantly increases the survival of new-born neurons (Kempermann et al, 1997;Körholz et al, 2018) by mechanisms involving neuronal activation in the hippocampus (Kirschen et al, 2017). We have previously shown that ENR changes DNA methylation patterns at neuronal plasticity genes in the dentate gyrus (Zocher et al, 2020). We here analyzed whether dynamic DNA methylation in NSPCs and immature neurons is required for the pro-neurogenic effect of ENR and for ENR-stimulated hippocampal excitability.…”

“…A functional role of DNA methylation changes during adult neurogenesis has previously been suggested by the disruption of the process through knock-out of the demethylating enzymes Tet1 and Tet2 as well as the methylation readers Mbd1 and Mecp2 (Gontier et al, 2018;Jobe et al, 2017;Li et al, 2014;Zhang et al, 2013). Moreover, both the neurogenic activity of adult hippocampal stem cells as well as brain DNA methylation patterns are sensitive to environmental stimuli and behavioral activity (Van Praag et al, 2000;Zocher et al, 2020). This makes DNA methylation an exciting potential mechanism underlying experience-dependent brain plasticity.…”