title: Spine growth in the anterior cingulate cortex is necessary for the consolidation of contextual fear memory.
abstract: Remodeling of cortical connectivity is thought to allow initially hippocampus-dependent memories to be expressed independently of the hippocampus at remote time points. Consistent with this, consolidation of a contextual fear memory is associated with dendritic spine growth in neurons of the anterior cingulate cortex (aCC). To directly test whether such cortical structural remodeling is necessary for memory consolidation, we disrupted spine growth in the aCC at different times following contextual fear conditioning in mice. We took advantage of previous studies showing that the transcription factor myocyte enhancer factor 2 (MEF2) negatively regulates spinogenesis both in vitro and in vivo. We found that increasing MEF2-dependent transcription in the aCC during a critical posttraining window (but not at later time points) blocked both the consolidation-associated dendritic spine growth and subsequent memory expression. Together, these data strengthen the causal link between cortical structural remodeling and memory consolidation and, further, identify MEF2 as a key regulator of these processes.
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
authors.forename: Gisella
authors.initials: G
authors.lastname: Vetere
authors.forename: Leonardo
authors.initials: L
authors.lastname: Restivo
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Cole
authors.forename: P Joel
authors.initials: PJ
authors.lastname: Ross
authors.forename: Martine
authors.initials: M
authors.lastname: Ammassari-Teule
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology*; D006179:Gyrus Cinguli / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D064326:MEF2 Transcription Factors; D051379:Mice; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D009474:Neurons / Q000648:ultrastructure; D014158:Transcription, Genetic
chemical_list: D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors