Journal
SCIENCE
Volume 311, Issue 5763, Pages 1008-1012Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1122511
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Funding
- NEI NIH HHS [R01 EY013613] Funding Source: Medline
- NIA NIH HHS [AG05870] Funding Source: Medline
- NICHD NIH HHS [HD18655] Funding Source: Medline
- NINDS NIH HHS [NS28829] Funding Source: Medline
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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.
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