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.
Highlights
Environmental experiences exert significant influence onto the complex genetic programs that drive neurodevelopment
To begin to address this gap in understanding, we recently showed that continuous EE during a critical period of intervention was sufficient to ameliorate subcortical white matter (WM) dysmyelination and recover motor deficits caused by perinatal hypoxic brain injury (Forbes et al, 2020)
After additional time spent in EE, these molecular changes translated into altered OL lineage cell dynamics, enhanced myelination, and improvement in subcortical WM-dependent locomotor coordination. These findings indicate that normal developmental myelination is susceptible to experience-dependent adaptation, thereby providing further evidence of myelin plasticity in the central nervous system (CNS)
Summary
Environmental experiences exert significant influence onto the complex genetic programs that drive neurodevelopment. Seminal work using monocular deprivation highlights the impact of experiential stimuli on postnatal neurodevelopment (Wiesel and Hubel, 1963). For over 50 years, environmental enrichment (EE) —an experimental paradigm that exposes animals to increased social interactions, novel stimuli, and voluntary exercise—has been used to study the role of Prolonged Environmental Enrichment experiential stimuli in brain health and disease (Diamond et al, 1964; van Praag et al, 2000). While neurological effects of EE are well-characterized in the adult brain, the impact of EE on the developing brain has not been widely explored outside of the visual system (Cancedda et al, 2004). EE research has primarily focused on neuronal and synaptic changes, despite critical roles of glial cells in neuroplasticity
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have