Journal Article

Neuronal Activity Promotes Oligodendrogenesis and Adaptive Myelination in the Mammalian Brain

Miller, Sarah E., Bieri, Gregor, Wood, Lauren S., Goldstein, Andrea K., Gibson, Erin M., Monje, Michelle, Lin, Grant L., Mount, Christopher W., Inema, Ingrid, Zuchero, J. Bradley, Barres, Ben A., Vogel, Hannes, Purger, David, Woo, Pamelyn J.

2014

Overview

Oligodendroglia ensheath axons in the brain with myelin, which provides the insulation that speeds up transmission of neuronal electrical impulses. The process of myelination in the human brain goes on for decades, concurrent with all manner of brain development and cognitive activity. Gibson et al. (p. 10.1126/science.1252304 , published online 10 April; see the Perspective by Bechler and ffrench-Constant ) used optogenetics to study myelination in response to neural activity. Electrical activity in the motor cortex of the brain of awake mice led to proliferation and differentiation of oligodendrocytes and consequently increased myelination and alterations in motor response. Optogenetic stimulation of the mouse motor cortex incites proliferation of myelin-producing cells and axonal myelination. [Also see Perspective by Bechler and ffrench-Constant ] Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity–regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.

• Publisher: American Association for the Advancement of Science
• Subject: Animals / Behavior, Animal - physiology / Cell Differentiation / Cell Lineage / Cell Proliferation / Channelrhodopsins / Corpus Callosum - cytology / Corpus Callosum - physiology / Mice / Mice, Mutant Strains / Motor Activity - physiology / Motor Cortex - cytology / Motor Cortex - physiology / Myelin Sheath - metabolism / Nerve Fibers, Myelinated - metabolism / Neural Stem Cells - physiology / Neurons - physiology / Oligodendroglia - cytology / RESEARCH ARTICLE SUMMARY / Thy-1 Antigens - genetics