Early myelination involves the dynamic and repetitive ensheathment of axons which resolves through a low and consistent stabilization rate

  1. Adam Raymond Almeida
  2. Wendy B Macklin  Is a corresponding author
  1. University of Colorado Anschutz Medical Campus, United States

Abstract

Oligodendrocytes in the central nervous system exhibit significant variability in the number of myelin sheaths that are supported by each cell, ranging from 1-50 (1-8). Myelin production during development is dynamic and involves both sheath formation and loss (3, 9-13). However, how these parameters are balanced to generate this heterogeneity in sheath number has not been thoroughly investigated. To explore this question, we combined extensive time-lapse and longitudinal imaging of oligodendrocytes in the developing zebrafish spinal cord to quantify sheath initiation and loss. Surprisingly, we found that oligodendrocytes repetitively ensheathed the same axons multiple times before any stable sheaths were formed. Importantly, this repetitive ensheathment was independent of neuronal activity. At the level of individual oligodendrocytes, each cell initiated a highly variable number of total ensheathments. However, ~80-90% of these ensheathments always disappeared, an unexpectedly high, but consistent rate of loss. The dynamics of this process indicated rapid membrane turn-over as ensheathments were formed and lost repetitively on each axon. To better understand how these sheath initiation dynamics contribute to the overall stabilization rate we disrupted membrane recycling by expressing a dominant-negative mutant form of Rab5. Oligodendrocytes over-expressing this mutant did not show a change in early sheath initiation dynamics but did lose a higher percentage of ensheathments in the later stabilization phase. Overall, oligodendrocyte sheath number is heterogeneous because each cell repetitively initiates a variable number of total ensheathments that are resolved through a consistent stabilization rate.

Data availability

All datasets generated and analyzed during this study are included in the manuscript.

Article and author information

Author details

  1. Adam Raymond Almeida

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9249-6688
  2. Wendy B Macklin

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    wendy.macklin@cuanschutz.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1252-0607

Funding

NIH Office of the Director (5F31NS118830)

  • Adam Raymond Almeida

NIH Office of the Director (R37NS82203)

  • Wendy B Macklin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The Institutional Animal Care and Use Committee at the University of Colorado School of Medicine approved all animal work (#00419). This group follows the U.S. National Research Council's Guide for the Care and Use of Laboratory Animals and the U.S. Public Health Service's Policy on Humane Care and Use of Laboratory Animals.

Copyright

© 2023, Almeida & Macklin

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,155
    views
  • 179
    downloads
  • 12
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Adam Raymond Almeida
  2. Wendy B Macklin
(2023)
Early myelination involves the dynamic and repetitive ensheathment of axons which resolves through a low and consistent stabilization rate
eLife 12:e82111.
https://doi.org/10.7554/eLife.82111

Share this article

https://doi.org/10.7554/eLife.82111

Further reading

    1. Neuroscience
    Célian Bimbard, Flóra Takács ... Philip Coen
    Tools and Resources

    Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) allow reuse of the probes after explantation; (3) be light enough for use in mice. Here, we present the ‘Apollo Implant’, an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a ‘payload’ module which is attached to the probe and is recoverable, and a ‘docking’ module which is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across eight labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.

    1. Neuroscience
    Georgin Jacob, RT Pramod, SP Arun
    Research Article

    Most visual tasks involve looking for specific object features. But we also often perform property-based tasks where we look for specific property in an image, such as finding an odd item, deciding if two items are same, or if an object has symmetry. How do we solve such tasks? These tasks do not fit into standard models of decision making because their underlying feature space and decision process is unclear. Using well-known principles governing multiple object representations, we show that displays with repeating elements can be distinguished from heterogeneous displays using a property we define as visual homogeneity. In behavior, visual homogeneity predicted response times on visual search, same-different and symmetry tasks. Brain imaging during visual search and symmetry tasks revealed that visual homogeneity was localized to a region in the object-selective cortex. Thus, property-based visual tasks are solved in a localized region in the brain by computing visual homogeneity.