title: MEF2 negatively regulates learning-induced structural plasticity and memory formation.
abstract: Memory formation is thought to be mediated by dendritic-spine growth and restructuring. Myocyte enhancer factor 2 (MEF2) restricts spine growth in vitro, suggesting that this transcription factor negatively regulates the spine remodeling necessary for memory formation. Here we show that memory formation in adult mice was associated with changes in endogenous MEF2 levels and function. Locally and acutely increasing MEF2 function in the dentate gyrus blocked both learning-induced increases in spine density and spatial-memory formation. Increasing MEF2 function in amygdala disrupted fear-memory formation. We rescued MEF2-induced memory disruption by interfering with AMPA receptor endocytosis, suggesting that AMPA receptor trafficking is a key mechanism underlying the effects of MEF2. In contrast, decreasing MEF2 function in dentate gyrus and amygdala facilitated the formation of spatial and fear memory, respectively. These bidirectional effects indicate that MEF2 is a key regulator of plasticity and that relieving the suppressive effects of MEF2-mediated transcription permits memory formation.
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Cole
authors.forename: Valentina
authors.initials: V
authors.lastname: Mercaldo
authors.forename: Leonardo
authors.initials: L
authors.lastname: Restivo
authors.forename: Adelaide P
authors.initials: AP
authors.lastname: Yiu
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Sekeres
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Han
authors.forename: Gisella
authors.initials: G
authors.lastname: Vetere
authors.forename: Tetyana
authors.initials: T
authors.lastname: Pekar
authors.forename: P Joel
authors.initials: PJ
authors.lastname: Ross
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Neve
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D003213:Conditioning, Psychological / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology; D000229:Dependovirus; D004705:Endocytosis / Q000502:physiology; D005239:Fear; D005260:Female; D005822:Genetic Vectors; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007858:Learning / Q000502:physiology*; D008156:Luciferases / Q000235:genetics; D064326:MEF2 Transcription Factors; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D018139:Simplexvirus / Q000235:genetics
chemical_list: D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D018091:Receptors, AMPA; D008156:Luciferases