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

doi:10.1126/science.1122511

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 journal › Article › peer-review

465 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 language	English (US)
Pages (from-to)	1008-1012
Number of pages	5
Journal	Science
Volume	311
Issue number	5763
DOIs	https://doi.org/10.1126/science.1122511
State	Published - Feb 17 2006

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title = "Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number",

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.",

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

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doi = "10.1126/science.1122511",

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T1 - Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number

AU - Flavell, Steven W.

AU - Cowan, Christopher W.

AU - Kim, Tae Kyung

AU - Greer, Paul L.

AU - Lin, Yingxi

AU - Paradis, Suzanne

AU - Griffith, Eric C.

AU - Hu, Linda S.

AU - Chen, Chinfei

AU - Greenberg, Michael E.

PY - 2006/2/17

Y1 - 2006/2/17

N2 - 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.

AB - 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.

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

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