title: Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity.
abstract: 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.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Ling-jie
authors.initials: LJ
authors.lastname: He
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xin-jie-kou-wai Road, Beijing 100875, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Tian-lin
authors.initials: TL
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xin-jie-kou-wai Road, Beijing 100875, China.
authors.forename: Xiao-jing
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Yi-ding
authors.initials: YD
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xin-jie-kou-wai Road, Beijing 100875, China.
authors.forename: You-sheng
authors.initials: YS
authors.lastname: Shu
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Zi-long
authors.initials: ZL
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xin-jie-kou-wai Road, Beijing 100875, China.
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003423:Critical Period, Psychological; D003433:Crosses, Genetic; D003975:Diazepam / Q000494:pharmacology; D005434:Flow Cytometry; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D007150:Immunohistochemistry; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D060888:Real-Time Polymerase Chain Reaction; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology*
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D010320:Parvalbumins; D003975:Diazepam