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Science. 2006 Feb 17;311(5763):1008-12.

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

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

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.

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PMID:
16484497
[PubMed - indexed for MEDLINE]
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