Intrinsic and adaptive myelination—A sequential mechanism for smart wiring in the brain

Abstract

The concept of adaptive myelination—myelin plasticity regulated by activity—is an important advance for the field. What signals set up the adaptable pattern in the first place? Here we review work that demonstrates an intrinsic pathway within oligodendrocytes requiring only an axon‐shaped substrate to generate multilayered and compacted myelin sheaths of a physiological length. Based on this, we discuss a model we proposed in 2015 which argues that myelination has two phases—intrinsic and then adaptive—which together generate “smart wiring,” in which active axons become more myelinated. This model explains why prior studies have failed to identify a signal necessary for central nervous system myelination and argues that myelination, like synapses, might contribute to learning by the activity‐dependent modification of an initially hard‐wired pattern. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 68–79, 2018

Length of myelin internodes of individual oligodendrocytes is controlled by microenvironment influenced by normal and input‐deprived axonal activities in sensory deprived mouse models

“…A study using in vitro oligodendrocyte culture prepared from the mouse spinal cord and cortex indicates that the length and number of myelin sheaths produced by individual oligodendrocytes are intrinsically determined independent of axon-derived molecules, suggesting that neuronal activity impacts on myelination following the initial sheath formation (Bechler et al, 2015(Bechler et al, , 2018. Our results also suggest that oligodendrocytes myelinate any subtype of axon, but neuronal activity regulates the number and morphology of myelin sheaths after initial myelination.…”

Low‐intensity transcranial magnetic stimulation promotes the survival and maturation of newborn oligodendrocytes in the adult mouse brain

“…Internode length and the number of internodes elaborated by individual oligodendrocytes differs between CNS regions (Butt, Colquhoun, Tutton, & Berry, ; Chong et al, ; Murtie, Macklin, & Corfas, ; Osanai et al, ; Tripathi et al, ; Young et al, ), and is determined by a combination of signals that are both intrinsic and extrinsic to the developing oligodendrocyte (Almeida, Czopka, & Lyons, ; Bechler, Byrne, & Ffrench‐Constant, ; Hines et al, ; reviewed by Bechler et al, ). Extrinsic signals, such as increased NogoA‐signaling (Chong et al, ), decreased neurotransmitter release (Mensch et al, ) and social isolation, which reduces Neuregulin‐ErbB3 receptor signaling (Makinodan, Rosen, Ito, & Corfas, ), can reduce the number of myelin internodes elaborated by individual oligodendrocytes.…”

“…Myelinating oligodendrocytes are added to the central nervous system (CNS) throughout life, generated from immature, proliferative oligodendrocyte progenitor cells (OPCs), also known as NG2‐glia (reviewed by Pepper, Pitman, Cullen, & Young, ). In development and adulthood, myelination is regulated by many intrinsic and extrinsic factors, with neuronal activity being a major extrinsic regulator of adaptive myelination (reviewed by Bechler, Swire, & Ffrench‐Constant, ), influencing OPC proliferation (Barres & Raff, ; Gibson et al, ), oligodendrogenesis (Gibson et al, ; Li, Brus‐Ramer, Martin, & McDonald, ), oligodendrocyte survival (Barres, Jacobson, Schmid, Sendtner, & Raff, ; Kougioumtzidou et al, ), myelin sheath stabilization (Hines, Ravanelli, Schwindt, Scott, & Appel, ), the number of internodes supported per oligodendrocyte (Mensch et al, ), and myelin sheath thickness (Gibson et al, ). The ability of neuronal activity to promote oligodendrogenesis and myelination also makes it an interesting therapeutic target for myelin repair.…”

Axoglial interactions in myelin plasticity: Evaluating the relationship between neuronal activity and oligodendrocyte dynamics

“…It is possible that the lack of preference for myelinating active axons in the above monocular deprivation experiments (Etxeberria et al, ; Osanai et al, ) reflects a dominant genetic program for myelination in the retinogeniculate pathway, which is nearly fully myelinated within the first month or two of life. (see Bechler, Swire, & ffrench‐Constant, , for further discussion of the potential for distinct default and activity‐dependent programs of myelination.) Nevertheless, Osanai et al () obtained similar results with reduced activity in a subset of somatosensory neurons via unilateral whisker trimming.…”

“…(see Bechler, Swire, & ffrench-Constant, 2017, for further discussion of the potential for distinct default and activity-dependent programs of myelination.) Nevertheless, Osanai et al (2018) obtained similar results with reduced activity in a subset of somatosensory neurons via unilateral whisker trimming.…”