title: Electrophysiological phenotypes of MeCP2 A140V mutant mouse model.
abstract: OBJECTIVE
  MeCP2 gene mutations are associated with Rett syndrome and X-linked mental retardation (XLMR), diseases characterized by abnormal brain development and function. Recently, we created a novel MeCP2 A140V mutation mouse model that exhibited abnormalities of cell packing density and dendritic branching consistent with that seen in Rett syndrome patients as well as other MeCP2 mutant mouse models. Therefore, we hypothesized that some deficits of neuronal and synaptic functions might also be present in the A140V mutant model.
  
  
  METHODS
  Here, we tested our hypothesis in hippocampal slices using electrophysiological recordings.
  
  
  RESULTS
  We found that in young A140V mutant mice (3- to 4-week-old), hippocampal CA1 pyramidal neurons exhibited more positive resting membrane potential, increased action potential (AP) firing frequency induced by injection of depolarizing current, wider AP duration, and smaller after hyperpolarization potential compared to neurons prepared from age-matched wild-type mice, suggesting a neuronal hyperexcitation. At the synaptic level, A140V mutant neurons exhibited a reduced frequency of spontaneous IPSCs (inhibitory postsynaptic potentials) and an enhanced probability of evoked glutamate release, both suggesting neuronal hyperexcitation. However, hippocampal CA1 long-term potentiation was not significantly different between A140V and WT mice. In adult mice (11- to 13-month-old), in addition to neuronal hyperexcitation, we also found significant deficits of both short-term and long-term potentiation of CA3-CA1 synapses in A140V mice compared to WT mice.
  
  
  CONCLUSIONS
  These results clearly illustrate the age-dependent abnormalities of neuronal and synaptic function in the MeCP2 A140V mutant mouse model, which provides new insights into the understanding of the pathogenesis of Rett syndrome.
authors.forename: Lu-Yao
authors.initials: LY
authors.lastname: Ma
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Li
authors.forename: Dharshaun
authors.initials: D
authors.lastname: Turner
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Shen
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Vinodh
authors.initials: V
authors.lastname: Narayanan
authors.forename: Garilyn
authors.initials: G
authors.lastname: Jentarra
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D010641:Phenotype; D015518:Rett Syndrome; D009435:Synaptic Transmission / Q000502:physiology; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
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