title: RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function.
abstract: RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders.
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Han-Ying
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: De-Fong
authors.initials: DF
authors.lastname: Huang
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Pey-Shyuan
authors.initials: PS
authors.lastname: Chin
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Chih-Hsuan
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Chun-Che
authors.initials: CC
authors.lastname: Tung
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Shin-Yuan
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.|Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.|Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.|Clinical Center for Neuroscience and Behavior, National Taiwan University Hospital, Taipei, 10002, Taiwan.|Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.|Ph.D. of Translational Medicine Program, National Taiwan University and Academia Sinica, Taipei, 10617, Taiwan.|Clinical Center for Neuroscience and Behavior, National Taiwan University Hospital, Taipei, 10002, Taiwan.|Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Hsien-Sung
authors.initials: HS
authors.lastname: Huang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D051765:Early Growth Response Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051765:Early Growth Response Transcription Factors; C486392:Egr4 protein, mouse; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; C092069:activity regulated cytoskeletal-associated protein