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      Myelin remodeling through experience-dependent oligodendrogenesis in the adult somatosensory cortex

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          Abstract

          The generation of oligodendrocytes in the adult CNS provides a means to adapt the properties of circuits to changes in life experience. However, little is known about the dynamics of oligodendrocytes and the extent of myelin remodeling in the mature brain. Using longitudinal in vivo two photon imaging of oligodendrocytes and their progenitors in the mouse cerebral cortex, we show that myelination is an inefficient and extended process, with half of the final complement of oligodendrocytes generated after four months of age. Oligodendrocytes that successfully integrated formed novel sheaths on unmyelinated and sparsely myelinated axons, and were extremely stable, gradually changing the pattern of myelination. Sensory enrichment robustly increased oligodendrocyte integration, but did not change the length of existing sheaths. This experience-dependent enhancement of myelination in the mature cortex may accelerate information transfer in these circuits and strengthen the ability of axons to sustain activity by providing additional metabolic support.

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          Most cited references20

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          A gene expression atlas of the central nervous system based on bacterial artificial chromosomes.

          The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.
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            Biology of oligodendrocyte and myelin in the mammalian central nervous system.

            Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, their relationships to other neural cells, and functional neuroglial interactions under physiological conditions and in demyelinating diseases. One of the problems in studies of the CNS is to find components, i.e., markers, for the identification of the different cells, in intact tissues or cultures. In recent years, specific biochemical, immunological, and molecular markers have been identified. Many components specific to differentiating oligodendrocytes and to myelin are now available to aid their study. Transgenic mice and spontaneous mutants have led to a better understanding of the targets of specific dys- or demyelinating diseases. The best examples are the studies concerning the effects of the mutations affecting the most abundant protein in the central nervous myelin, the proteolipid protein, which lead to dysmyelinating diseases in animals and human (jimpy mutation and Pelizaeus-Merzbacher disease or spastic paraplegia, respectively). Oligodendrocytes, as astrocytes, are able to respond to changes in the cellular and extracellular environment, possibly in relation to a glial network. There is also a remarkable plasticity of the oligodendrocyte lineage, even in the adult with a certain potentiality for myelin repair after experimental demyelination or human diseases.
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              Myelination and support of axonal integrity by glia.

              The myelination of axons by glial cells was the last major step in the evolution of cells in the vertebrate nervous system, and white-matter tracts are key to the architecture of the mammalian brain. Cell biology and mouse genetics have provided insight into axon-glia signalling and the molecular architecture of the myelin sheath. Glial cells that myelinate axons were found to have a dual role by also supporting the long-term integrity of those axons. This function may be independent of myelin itself. Myelin abnormalities cause a number of neurological diseases, and may also contribute to complex neuropsychiatric disorders.
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                Author and article information

                Journal
                9809671
                21092
                Nat Neurosci
                Nat. Neurosci.
                Nature neuroscience
                1097-6256
                1546-1726
                22 February 2018
                19 March 2018
                May 2018
                19 September 2018
                : 21
                : 5
                : 696-706
                Affiliations
                [1 ]The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD
                [2 ]Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO
                [3 ]Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
                Author notes
                [+ ]Corresponding author: Correspondence to Dwight E. Bergles ( dbergles@ 123456jhmi.edu ) and Ethan G. Hughes ( ethan.hughes@ 123456ucdenver.edu )
                [*]

                Co-First Authors

                Article
                NIHMS945380
                10.1038/s41593-018-0121-5
                5920726
                29556025
                2ab3e671-3ab7-43fe-8ea1-c8fbb04765f6

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