Prolonged Environmental Enrichment Promotes Developmental Myelination

Abstract

Postnatal neurodevelopment is profoundly influenced by environmental experiences. Environmental enrichment is a commonly used experimental paradigm that has uncovered numerous examples of experience-dependent plasticity in health and disease. However, the role of environmental enrichment in normal development, especially glial development, is largely unexplored. Oligodendrocytes, the myelin-forming glia in the central nervous system, provide metabolic support to axons and establish efficient saltatory conduction by producing myelin. Indeed, alterations in myelin are strongly correlated with sensory, cognitive, and motor function. The timing of developmental myelination is uniquely positioned to be influenced by environmental stimuli, as peak myelination occurs postnatally and continues into adulthood. To determine if developmental myelination is impacted by environmental experience, mice were housed in an enriched environment during peak myelination through early adulthood. Using translating ribosome affinity purification, oligodendrocyte-specific RNAs were isolated from subcortical white matter at various postnatal ages. RNA-sequencing revealed that differences in the oligodendrocyte translatome were predominantly evident after prolonged and continuous environmental enrichment. These translational changes corresponded with altered oligodendrocyte lineage cell dynamics and enhanced myelination. Furthermore, consistent with increased developmental myelination, enriched mice displayed enhanced motor coordination on a beam walking task. These findings indicate that protracted environmental stimulation is sufficient to modulate developmental myelination and to promote behavioral function.

Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration

“…Reactive microglia also release TG2 which activates GPR56 and potentially reduces the susceptibility of preOLs to apoptosis (Giera et al, 2018). and generation of new oligodendrocytes during development and after hypoxic injury (Forbes et al, 2020;Goldstein et al, 2021; Figure 3). Furthermore, increasing neuronal activity via optogenetic stimulation increases OPC differentiation and increases the number of newly formed oligodendrocytes (Gibson et al, 2014; Figure 3).…”

“…Genetic fate mapping and post hoc immunostaining in slice cultures suggested whisker trimming led to decreased integration of oligodendrocytes ( Hill et al, 2014 ; Figure 3 ). On the other hand, increased sensory experience via environmental enrichment was found to promote the maturation and generation of new oligodendrocytes during development and after hypoxic injury ( Forbes et al, 2020 ; Goldstein et al, 2021 ; Figure 3 ). Furthermore, increasing neuronal activity via optogenetic stimulation increases OPC differentiation and increases the number of newly formed oligodendrocytes ( Gibson et al, 2014 ; Figure 3 ).…”

The role of enriched environment in neural development and repair

“…EE for 30 days did not initially increase oligodendrocytes and myelin expression in the white matter. Follow-up studies were surprised to find that 60 days of EE enhanced the g/ratio and more new myelinated axons in 90 days of EE, which suggests that the effects of EE on axons begin with the thickening of myelin fibers followed by an increase in the number of internodes (Goldstein et al, 2021 ). In addition, more oligodendrocyte progenitor cells proliferation and oligodendrocyte mature cells were detected in the sensorimotor cortex at 10 and 42 days of EE intervention, respectively (Keiner et al, 2017 ), which indicats EE will accelerate axon development.…”

Presentation and integration of multiple signals that modulate oligodendrocyte lineage progression and myelination

“…Single photostimulation, which robustly induces OPC proliferation (Gibson et al, 2014 ), may result in a moderate increase in OLs but may not be sufficient to allow progression to trigger the myelination program. Enhanced sensory experience has also been shown to promote OL maturation and differentiation (Forbes et al, 2020 ; Goldstein et al, 2021 ). How changes in neuronal activity are detected by NFOLs remains to be solved.…”