Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity
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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.
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Cell-specific, germ-line, and mosaic deletions of MeCP2 have different impacts on the developmental trajectory of cortical circuit assembly and function.
“Taken together, our results and previous studies (60,62) suggest that cell specific, germ-line, and mosaic deletions of MeCP2 have different impacts on the developmental trajectory of cortical circuit assembly and function;”
From MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex (2015) · cites this paper as [60]
A recent study using conditional deletion of MeCP2 in PV cells during the third to fourth postnatal week reported an absence of critical period plasticity.
“A recent study using conditional deletion of MeCP2 in PV cells during the third to fourth postnatal week reported an absence of critical period plasticity (60).”
From MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex (2015) · cites this paper as [60]
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- Authors
- He, L.-J., Liu, N., Cheng, T.-L., Chen, X.-J., Li, Y.-D., Shu, Y.-S., Qiu, Z.-L., & Zhang, X.-H.
- Affiliations
- Chinese Academy of Sciences (CN)
- Beijing Normal University (CN)
- Corresponding author
- Zhang, Xiao-hui
- ORCID
- Cheng, Tian-lin
- Venue
- Nature Communications
- Published
- 2014-10-09
- Volume
- 5
- Issue
- 1
- Pages
- 5036-5036
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1995939503
- Cited by
- 107
- References
- 65
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 14 · 2019: 12 · 2018: 14 · 2017: 10 · 2016: 11 · 2015: 8
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Key Research and Development Program of China (2011CBA00400, 2011CBA00403)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Keywords
- MeCP2, Rett syndrome, parvalbumin interneurons, GABAergic neurons, critical period plasticity, primary visual cortex, experience-dependent plasticity, somatostatin interneurons, pyramidal neurons, cortical excitability, diazepam, GABAergic inhibition, local cortical circuits
- MeSH terms
- Animals, Critical Period, Psychological, Crosses, Genetic, Diazepam, Flow Cytometry, Immunohistochemistry, Male, Mice, Inbred C57BL, Neuronal Plasticity, Parvalbumins, Photic Stimulation, Visual Cortex, Gene Deletion, Patch-Clamp Techniques, Microscopy, Confocal, Mice, Methyl-CpG-Binding Protein 2, GABAergic Neurons, Real-Time Polymerase Chain Reaction
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