title: NeonatalCX26removal impairs neocortical development and leads to elevated anxiety.
abstract: Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical coupling between neocortical excitatory neurons is critical for proper neuronal development, synapse formation, and animal behavior. Conditional deletion ofConnexin 26(CX26) in the superficial layer excitatory neurons of the mouse neocortex around birth significantly reduces spontaneous firing activity and the frequency and size of spontaneous network oscillations at postnatal day 5-6. Moreover,CX26-conditional knockout (CX26-cKO) neurons tend to have simpler dendritic trees and lower spine density compared with wild-type neurons. Importantly, early, but not late, postnatal deletion ofCX26, decreases the frequency of miniature excitatory postsynaptic currents (mEPSCs) in both young and adult mice, whereas miniature inhibitory postsynaptic currents (mIPSCs) were unaffected. Furthermore,CX26-cKO mice exhibit increased anxiety-related behavior. These results suggest that electrical coupling between excitatory neurons at early postnatal stages is a critical step for neocortical development and function.
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Lin-Yun
authors.initials: LY
authors.lastname: Liu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Li-Zhao
authors.initials: LZ
authors.lastname: Zhang
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Li
authors.affiliation: Centre for Computational Systems Biology and the School of Mathematical Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Xiang-Nan
authors.initials: XN
authors.lastname: He
authors.affiliation: Centre for Computational Systems Biology and the School of Mathematical Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Wenlian
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Otorhinolaryngology, Hearing Research Institute, Research Center, Affiliated Eye and Ear, Nose, and Throat Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200031, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Otorhinolaryngology, Hearing Research Institute, Research Center, Affiliated Eye and Ear, Nose, and Throat Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200031, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; ycyu@fudan.edu.cn.|Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Yu
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism* / Q000523:psychology; D001522:Behavior, Animal; D000072259:Connexin 26 / Q000235:genetics* / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019579:Neocortex / Q000378:metabolism* / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy
chemical_list: D000072259:Connexin 26
keywords: CX26; anxiety; development; neocortex