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

Science (New York, N.Y.) | Feb 17, 2006

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.

Pubmed ID: 16484497 RIS Download

Mesh terms: Animals | Calcineurin | Calcium | Cells, Cultured | Cytoskeletal Proteins | Dendrites | Excitatory Postsynaptic Potentials | GTPase-Activating Proteins | Gene Expression Regulation | Glutamic Acid | Hippocampus | MEF2 Transcription Factors | Mutation | Myogenic Regulatory Factors | Nerve Tissue Proteins | Neurons | Oligonucleotide Array Sequence Analysis | Phosphorylation | RNA Interference | Rats | Rats, Long-Evans | Recombinant Fusion Proteins | Synapses | Synaptic Transmission | Transcription, Genetic | Transfection

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Associated grants

  • Agency: NEI NIH HHS, Id: R01 EY013613
  • Agency: NIA NIH HHS, Id: AG05870
  • Agency: NICHD NIH HHS, Id: HD18655
  • Agency: NINDS NIH HHS, Id: NS28829

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