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

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-M...

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Published in:Nature communications 2014-10, Vol.5 (1), p.5036-5036, Article 5036
Main Authors: He, Ling-jie, Liu, Nan, Cheng, Tian-lin, Chen, Xiao-jing, Li, Yi-ding, Shu, You-sheng, Qiu, Zi-long, Zhang, Xiao-hui
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Language:English
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Summary: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. Critical period plasticity describes a developmental process whereby neural circuits are fine-tuned for specific functions. Here, the authors show that the Rett syndrome protein MeCP2 in GABAergic parvalbumin-expressing neurons is required for critical period plasticity of the visual cortex.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms6036