1. Neuroscience
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Astrocytic modulation of excitatory synaptic signaling in a mouse model of Rett syndrome

  1. Benjamin Rakela  Is a corresponding author
  2. Paul Brehm
  3. Gail Mandel  Is a corresponding author
  1. Oregon Health and Science University, United States
Research Article
  • Cited 12
  • Views 2,449
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Cite this article as: eLife 2018;7:e31629 doi: 10.7554/eLife.31629

Abstract

Studies linking mutations in Methyl CpG Binding Protein 2 (MeCP2) to physiological defects in the neurological disease, Rett syndrome, have focused largely upon neuronal dysfunction despite MeCP2 ubiquitous expression. Here we explore roles for astrocytes in neuronal network function using cortical slice recordings. We find that astrocyte stimulation in wild-type mice increases excitatory synaptic activity that is absent in male mice lacking MeCP2 globally. To determine the cellular basis of the defect, we exploit a female mouse model for Rett syndrome that expresses wild-type MeCP2-GFP in a mosaic distribution throughout the brain, allowing us to test all combinations of wild-type and mutant cells. We find that the defect is dependent upon MeCP2 expression status in the astrocytes and not in the neurons. Our findings highlight a new role for astrocytes in regulation of excitatory synaptic signaling and in the neurological defects associated with Rett syndrome.

Article and author information

Author details

  1. Benjamin Rakela

    Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    Rakela@ohsu.edu
    Competing interests
    No competing interests declared.
  2. Paul Brehm

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    No competing interests declared.
  3. Gail Mandel

    Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    mandelg@ohsu.edu
    Competing interests
    Gail Mandel, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4264-0562

Funding

National Institutes of Health (HD081037)

  • Paul Brehm
  • Gail Mandel

Rett Syndrome Research Trust (RSRT)

  • Gail Mandel

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 animal procedures were approved by the Oregon Health and Science University Institutional Animal Care and Use Committee under protocol number IP00000284.

Reviewing Editor

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

Publication history

  1. Received: August 30, 2017
  2. Accepted: January 8, 2018
  3. Accepted Manuscript published: January 9, 2018 (version 1)
  4. Version of Record published: January 17, 2018 (version 2)
  5. Version of Record updated: January 22, 2018 (version 3)

Copyright

© 2018, Rakela 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.

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