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Science 311 (5763): 1008-1012

Copyright © 2006 by the American Association for the Advancement of Science

Activity-Dependent Regulation of MEF2 Transcription Factors Suppresses Excitatory Synapse Number

Steven W. Flavell,1,2* Christopher W. Cowan,1*{dagger} Tae-Kyung Kim,1 Paul L. Greer,1 Yingxi Lin,1 Suzanne Paradis,1 Eric C. Griffith,1 Linda S. Hu,1 Chinfei Chen,1 Michael E. Greenberg1{ddagger}

Abstract: In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated MEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.

1 Neurobiology Program, Children's Hospital, and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2 Program in Neuroscience, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390–9070, USA.

{ddagger} To whom correspondence should be addressed. E-mail: michael.greenberg{at}childrens.harvard.edu

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