Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone

  1. Elizabeth A Gould
  2. Nicolas Busquet
  3. Douglas Shepherd
  4. Robert Dietz
  5. Paco S Herson
  6. Fabio M Simoes de Souza
  7. Anan Li
  8. Nicholas M George
  9. Diego Restrepo  Is a corresponding author
  10. Wendy B Macklin  Is a corresponding author
  1. University of Colorado Anschutz Medical Campus, United States
  2. Federal University of ABC, Brazil
  3. Xuzhou Medical University, China

Abstract

Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/ maintenance is disrupted. Axon disruption occurs in Plp1-null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1-null mice. Young adult Plp1-null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption.

Article and author information

Author details

  1. Elizabeth A Gould

    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.
  2. Nicolas Busquet

    Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Douglas Shepherd

    Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Robert Dietz

    Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Paco S Herson

    Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Fabio M Simoes de Souza

    Center of Mathematics, Computation and Cognition, Federal University of ABC, Sao Bernardo do Campo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  7. Anan Li

    Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Nicholas M George

    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.
  9. Diego Restrepo

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    Diego.Restrepo@ucdenver.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4972-446X
  10. Wendy B Macklin

    Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    wendy.macklin@ucdenver.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

National Institutes of Health (NS25304)

  • Wendy B Macklin

National Multiple Sclerosis Society

  • Wendy B Macklin

National Institutes of Health (DC00566)

  • Diego Restrepo

National Institutes of Health (DC014253)

  • Diego Restrepo

National Institutes of Health (AG053690)

  • Douglas Shepherd

National Institutes of Health (DC012280)

  • Elizabeth A Gould

National Institutes of Health (NS099042)

  • Elizabeth A Gould

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

Ethics

Animal experimentation: All animals used in this study were treated in accordance with the University of Colorado Animal Care and Use Committee guidelines. The University of Colorado Animal Care and Use Committee approved this study under protocol numbers B-39615(05)1E and 00134.

Reviewing Editor

  1. Beth Stevens, Boston Children's Hospital, Harvard Medical School, United States

Publication history

  1. Received: January 4, 2018
  2. Accepted: February 1, 2018
  3. Accepted Manuscript published: February 13, 2018 (version 1)
  4. Version of Record published: February 27, 2018 (version 2)

Copyright

© 2018, Gould et al.

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

  • 2,631
    Page views
  • 415
    Downloads
  • 26
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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. Elizabeth A Gould
  2. Nicolas Busquet
  3. Douglas Shepherd
  4. Robert Dietz
  5. Paco S Herson
  6. Fabio M Simoes de Souza
  7. Anan Li
  8. Nicholas M George
  9. Diego Restrepo
  10. Wendy B Macklin
(2018)
Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone
eLife 7:e34783.
https://doi.org/10.7554/eLife.34783

Further reading

    1. Neuroscience
    Andrea Alamia, Lucie Terral ... Rufin VanRullen
    Research Article Updated

    Previous research has associated alpha-band [8–12 Hz] oscillations with inhibitory functions: for instance, several studies showed that visual attention increases alpha-band power in the hemisphere ipsilateral to the attended location. However, other studies demonstrated that alpha oscillations positively correlate with visual perception, hinting at different processes underlying their dynamics. Here, using an approach based on traveling waves, we demonstrate that there are two functionally distinct alpha-band oscillations propagating in different directions. We analyzed EEG recordings from three datasets of human participants performing a covert visual attention task (one new dataset with N = 16, two previously published datasets with N = 16 and N = 31). Participants were instructed to detect a brief target by covertly attending to the screen’s left or right side. Our analysis reveals two distinct processes: allocating attention to one hemifield increases top-down alpha-band waves propagating from frontal to occipital regions ipsilateral to the attended location, both with and without visual stimulation. These top-down oscillatory waves correlate positively with alpha-band power in frontal and occipital regions. Yet, different alpha-band waves propagate from occipital to frontal regions and contralateral to the attended location. Crucially, these forward waves were present only during visual stimulation, suggesting a separate mechanism related to visual processing. Together, these results reveal two distinct processes reflected by different propagation directions, demonstrating the importance of considering oscillations as traveling waves when characterizing their functional role.

    1. Developmental Biology
    2. Neuroscience
    Kenneth Kin Lam Wong, Tongchao Li ... Liqun Luo
    Research Article

    How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.