title: Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory.
abstract: Myocyte enhancer factor 2 (MEF2) transcription factors play critical roles in diverse cellular processes during central nervous system development. Studies attempting to address the role of MEF2 in brain have largely relied on overexpression of a constitutive MEF2 construct that impairs memory formation or knockdown of MEF2 function that increases spine numbers and enhances memory formation. Genetic deletion of individual MEF2 isoforms in brain during embryogenesis demonstrated that Mef2c loss negatively regulates spine numbers resulting in learning and memory deficits, possibly as a result of its essential role in development.
  
  
  
  To investigate MEF2C function in brain further, we genetically deleted Mef2c during postnatal development in mice. We characterized these conditional Mef2c knockout mice in an array of behavioral paradigms and examined the impact of postnatal loss of Mef2c on long-term potentiation.
  
  
  
  We observed increased spine numbers in hippocampus of the conditional Mef2c knockout mice. However, the postnatal loss of Mef2c did not impact learning and memory, long-term potentiation, or social and repetitive behaviors.
  
  
  
  Our findings demonstrate a critical role for MEF2C in the regulation of spine numbers with a dissociation of learning and memory, synaptic plasticity, and measures of autism-related behaviors in postnatal brain.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Megumi
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Heena
authors.initials: H
authors.lastname: Pranav
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: lisa.monteggia@utsouthwestern.edu.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Monteggia
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology*; D049229:Dendritic Spines; D004195:Disease Models, Animal; D007858:Learning / Q000502:physiology*; D064326:MEF2 Transcription Factors; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*
chemical_list: D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse
keywords: Autism; Behavior; Fear conditioning; MEF2C; Postnatal brain; Synaptic plasticity