title: MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function.
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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Barbosa
authors.forename: Mi-Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Mert
authors.initials: M
authors.lastname: Ertunc
authors.forename: Megumi
authors.initials: M
authors.lastname: Adachi
authors.forename: Erika D
authors.initials: ED
authors.lastname: Nelson
authors.forename: John
authors.initials: J
authors.lastname: McAnally
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Monteggia
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000648:ultrastructure; D017353:Gene Deletion; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D017774:Long-Term Potentiation; D064326:MEF2 Transcription Factors; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D019580:Perforant Pathway / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D017405:Herpes Simplex Virus Protein Vmw65; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors