MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function

Ana C. Barbosa, Mi Sung Kim, Mert Ertunc, Megumi Adachi, Erika D. Nelson, John McAnally, James A Richardson, Ege T Kavalali, Lisa M Monteggia, Rhonda S Bassel-Duby, Eric N Olson

Research output: Contribution to journalArticle

164 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9391-9396
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number27
DOIs
StatePublished - Jul 8 2008

Keywords

  • Learning deficits
  • Synaptic transmission
  • Synaptogenesis

ASJC Scopus subject areas

  • General

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