Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior

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Abstract

Rett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene MECP2. Mutations of Mecp2 restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a pathophysiological role for inhibitory interneurons. Recent work has suggested that vasoactive intestinal peptide-expressing (VIP) interneurons may play a critical role in the proper development and function of cortical circuits, making them a potentially key point of vulnerability in neurodevelopmental disorders. However, little is known about the role of VIP interneurons in Rett Syndrome. Here we find that loss of MeCP2 specifically from VIP interneurons replicates key neural and behavioral phenotypes observed following global Mecp2 loss of function.

Data availability

Source data files are included for each figure and supplemental figure. Analysis code is available at https://github.com/jesscardin/Miri-Vinck-et-al. All data included in this study will be freely available upon request, as the data files and associated intermediate analysis files are very large (400GB) and depositing the full data is not feasible.

Article and author information

Author details

James M Mossner

Department of Neuroscience, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Renata Batista-Brito

Department of Neuroscience, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Rima Pant

Department of Neuroscience, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Jessica A Cardin

Department of Neuroscience, Yale University, New Haven, United States

For correspondence
jess.cardin@yale.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8209-5466

Funding

Simons Foundation (SFARI)

Jessica A Cardin

National Institute of Mental Health (MH113852)

Jessica A Cardin

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were approved by the Institutional Animal Care and Use Committee of Yale University (#11317).

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.