The Rett Syndrome Protein MeCP2 Regulates Synaptic Scaling
- Zilong Qiu1,3,*,
- Emily L. Sylwestrak1,*,
- David N. Lieberman2,
- Yan Zhang3,
- Xin-Yu Liu3, and
- Anirvan Ghosh1
- 1Neurobiology Section, Division of Biological Sciences, and
- 2Department of Neurosciences, University of California, San Diego, La Jolla, California 92093-0366, and
- 3Institute of Neuroscience, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
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Author contributions: Z.Q., E.L.S., D.N.L., and A.G. designed research; Z.Q., E.L.S., D.N.L., Y.Z., and X.-Y.L. performed research; Z.Q., E.L.S., D.N.L., Y.Z., and X.-Y.L. analyzed data; Z.Q., E.L.S., and A.G. wrote the paper.
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↵*Z.Q. and E.L.S. contributed equally to this work.
Abstract
Synaptic scaling is a form of homeostatic synaptic plasticity characterized by cell-wide changes in synaptic strength in response to changes in overall levels of neuronal activity. Here we report that bicuculline-induced increase in neuronal activity leads to a decrease in mEPSC amplitude and a decrease in expression of the AMPA receptor subunit GluR2 in rat hippocampal cultures. Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A. Downregulation of MeCP2 by shRNA expression or genetic deletion blocks the bicuculline-induced decrease in GluR2 expression and mEPSC amplitude. These observations indicate that MeCP2 mediates activity-dependent synaptic scaling, and suggest that the pathophysiology of Rett syndrome, which is caused by mutations in MeCP2, may involve defects in activity-dependent regulation of synaptic currents.
- Received January 11, 2011.
- Revision received November 12, 2011.
- Accepted November 17, 2011.
- Copyright © 2012 the authors 0270-6474/12/320989-06$15.00/0
