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PMID:18599438

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Citation

Barbosa, AC, Kim, MS, Ertunc, M, Adachi, M, Nelson, ED, McAnally, J, Richardson, JA, Kavalali, ET, Monteggia, LM, Bassel-Duby, R and Olson, EN (2008) MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function. Proc. Natl. Acad. Sci. U.S.A. 105:9391-6

Abstract

Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal-dependent learning and memory.

Links

PubMed PMC2453723 Online version:10.1073/pnas.0802679105

Keywords

Animals; Dendritic Spines/metabolism; Dentate Gyrus/metabolism; Dentate Gyrus/ultrastructure; Gene Deletion; Herpes Simplex Virus Protein Vmw65/metabolism; Long-Term Potentiation; Memory/physiology; Mice; Mice, Transgenic; Mutation/genetics; Myogenic Regulatory Factors/genetics; Myogenic Regulatory Factors/metabolism; Organ Specificity; Perforant Pathway/metabolism; Synapses/metabolism; Synapses/ultrastructure; Synaptic Transmission; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MEF2C

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:2000310: regulation of NMDA receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0051966: regulation of synaptic transmission, glutamatergic

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0051963: regulation of synapse assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0046928: regulation of neurotransmitter secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0060998: regulation of dendritic spine development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0060079: excitatory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0007611: learning or memory

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0060025: regulation of synaptic activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0046928: regulation of neurotransmitter secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0051963: regulation of synapse assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0051966: regulation of synaptic transmission, glutamatergic

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0060079: excitatory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:0060998: regulation of dendritic spine development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:2000310: regulation of NMDA receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0001885)

Seeded From UniProt

complete

MOUSE:MEF2C

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0001885)

Seeded From UniProt

complete


See also

References

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