Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity

Nat Commun. 2014 Oct 9:5:5036. doi: 10.1038/ncomms6036.


Mutations in the X-linked gene encoding the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2) impair postnatal development of the brain. Here we use neuronal-type specific gene deletion in mice to show that conditional Mecp2 deletion in GABAergic parvalbumin-expressing (PV) cells (PV-Mecp2(-/y)) does not cause most Rett-syndrome-like behaviours, but completely abolishes experience-dependent critical period plasticity of primary visual cortex (V1) that develops normal visual functions. However, selective loss of Mecp2 in GABAergic somatostatin-expressing cells or glutamatergic pyramidal cells does not affect the critical period plasticity. MeCP2-deficient PV cells exhibit high intrinsic excitability, selectively reduced efficacy of recurrent excitatory synapses in V1 layer 4 circuits, and decreased evoked visual responses in vivo. Enhancing cortical gamma-aminobutyric acid (GABA) inhibition with diazepam infusion can restore critical period plasticity in both young and adult PV-Mecp2(-/y) mice. Thus, MeCP2 expression in inhibitory PV cells during the critical period is essential for local circuit functions underlying experience-dependent cortical plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Critical Period, Psychological*
  • Crosses, Genetic
  • Diazepam / pharmacology
  • Flow Cytometry
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology*
  • Gene Deletion
  • Immunohistochemistry
  • Male
  • Methyl-CpG-Binding Protein 2 / deficiency*
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques
  • Photic Stimulation
  • Real-Time Polymerase Chain Reaction
  • Visual Cortex / cytology
  • Visual Cortex / physiology*


  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Parvalbumins
  • Diazepam