Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number

Steven W. Flavell, Christopher W. Cowan, Tae Kyung Kim, Paul L. Greer, Yingxi Lin, Suzanne Paradis, Eric C. Griffith, Linda S. Hu, Chinfei Chen, Michael E. Greenberg

Research output: Contribution to journalArticle

390 Scopus citations

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 ore and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.

Original languageEnglish (US)
Pages (from-to)1008-1012
Number of pages5
JournalScience
Volume311
Issue number5763
DOIs
StatePublished - Feb 17 2006

ASJC Scopus subject areas

  • General

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    Flavell, S. W., Cowan, C. W., Kim, T. K., Greer, P. L., Lin, Y., Paradis, S., Griffith, E. C., Hu, L. S., Chen, C., & Greenberg, M. E. (2006). Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science, 311(5763), 1008-1012. https://doi.org/10.1126/science.1122511