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

• 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
• Format: Article
• Language: English
• Subjects: 13/31; 14/69; 38/1; 38/77; 64/110; 692/420/2489/144; 692/699/375/366; 9/74; Animals; Critical Period (Psychology); Crosses, Genetic; Diazepam - pharmacology; Flow Cytometry; GABAergic Neurons - metabolism; GABAergic Neurons - physiology; Gene Deletion; Humanities and Social Sciences; Immunohistochemistry; Male; Methyl-CpG-Binding Protein 2 - deficiency; Methyl-CpG-Binding Protein 2 - genetics; Mice; Mice, Inbred C57BL; Microscopy, Confocal; multidisciplinary; Neuronal Plasticity - drug effects; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Parvalbumins - metabolism; Patch-Clamp Techniques; Photic Stimulation; Real-Time Polymerase Chain Reaction; Science; Science (multidisciplinary); Visual Cortex - cytology; Visual Cortex - physiology
• ISSN: 2041-1723; 2041-1723
• 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. 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.