Individual neuronal subtypes control initial myelin sheath growth and stabilization

Abstract

Background In the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors. Methods To address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes. Results In the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons. Conclusion We conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.

Regulation of myelination by microglia

“…The myelinating processes of a mature oligodendrocyte are guided by physical ( 32 ) and biochemical signals toward axons, selectively myelinating in a neuronal subtype–specific manner ( 33 ). Not all nerve axons are myelinated, and the extent of myelination varies greatly, even along an individual axon, within a neuronal subtype, or region of the brain ( 34 ).…”

Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth

“…Rohon-Beard neurons in the dorsal spinal cord project large axons accessible to oligodendrocyte processes 33 but that are essentially unmyelinated. 20 , 38 The frequency of SypHy events along Rohon-Beard axons was significantly lower than in reticulospinal neurons as a whole and comparable to not-yet myelinated reticulospinal axons ( Figures 3 H and 3I; Video S6 ). Taken together, these data indicate that, surprisingly, myelination itself promotes vesicular fusion along myelinated axons, revealing a novel role for myelin in regulating axonal physiology.…”

Deletion of the Sodium-Dependent Glutamate Transporter GLT-1 in Maturing Oligodendrocytes Attenuates Myelination of Callosal Axons During a Postnatal Phase of Central Nervous System Development

“…Such modulation of myelination is to be seen as an adaptive mechanism, also referred to as myelin plasticity, that finetunes developmental myelination by addition of new myelin and modifications to pre-existing myelin sheaths (Liu et al, 2012;Makinodan et al, 2012;Hill et al, 2018;Hughes et al, 2018;Bacmeister et al, 2020), and by complementing a socalled intrinsic process of myelination, which is thought to occur independently of axonal signals Bechler et al, 2015Bechler et al, , 2018Mayoral et al, 2018). The concept of adaptive myelination from the initial stages of myelination onward and regulated by the properties of individual axons is further supported by in vivo imaging studies done in the developing zebrafish (Hines et al, 2015;Mensch et al, 2015;Koudelka et al, 2016;Nelson et al, 2020). Importantly, the extent and timing of CNS myelination, and thus their modulation by electrical activity, contributes significantly to neuronal circuitry function and its behavioral outputs (Forbes and Gallo, 2017;Bonnefil et al, 2019;Suminaite et al, 2019;Liu et al, 2020;Moore et al, 2020;Pan et al, 2020;Steadman et al, 2020;Xin and Chan, 2020;Fletcher et al, 2021).…”