MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex

Keerthi Krishnan, Bor Shuen Wang, Jiangteng Lu, Lang Wang, Arianna Maffei, Jianhua Cang*, Z. Josh Huang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome, an autism spectrum-associated disorder with a host of neurological and sensory symptoms, but the pathogenic mechanisms remain elusive. Neuronal circuits are shaped by experience during critical periods of heightened plasticity. The maturation of cortical GABA inhibitory circuitry, the parvalbumin+ (PV+ )fast-spiking interneurons in particular, is a key component that regulates the initiation and termination of the critical period. Using MeCP2-null mice, we examined experience-dependent development of neural circuits in the primary visual cortex. The functional maturation of parvalbumin interneurons was accelerated upon vision onset, as indicated by elevated GABA synthetic enzymes, vesicular GABA transporter, perineuronal nets, and enhanced GABA transmission among PV interneurons. These changes correlated with a precocious onset and closure of critical period and deficient binocular visual function in mature animals. Reduction of GAD67 expression rescued the precocious opening of the critical period, suggesting its major role in MECP2-mediated regulation of experience-driven circuit development. Our results identify molecular changes in a defined cortical cell type and link aberrant developmental trajectory to functional deficits in a model of neuropsychiatric disorder.

Original languageEnglish (US)
Pages (from-to)E4782-E4791
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number34
DOIs
StatePublished - Aug 25 2015

Keywords

  • Critical period plasticity
  • MeCP2
  • Parvalbumin interneurons
  • Rett syndrome
  • Visual cortex

ASJC Scopus subject areas

  • General

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