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

Abstract
Article and author information
Metrics

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

Benjamin Rakela

Vollum Institute, Oregon Health and Science University, Portland, United States

For correspondence
Rakela@ohsu.edu

Competing interests
No competing interests declared.
Paul Brehm

Vollum Institute, Oregon Health and Science University, Portland, United States

Competing interests
No competing interests declared.
Gail Mandel

Vollum Institute, Oregon Health and Science University, Portland, United States

For correspondence
mandelg@ohsu.edu

Competing interests
Gail Mandel, Reviewing editor, eLife.

"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.

Copyright

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.