RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
Journal
Scientific Reports
Journal Volume
5
Pages
17383
Date Issued
2015
Author(s)
Wang H.-Y.
Hsieh P.-F.
Huang D.-F.
Chin P.-S.
Chou C.-H.
Tung C.-C.
Chen S.-Y.
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.
SDGs
Other Subjects
activity regulated cytoskeletal-associated protein; cytoskeleton protein; early growth response factor; Egr4 protein, mouse; nerve protein; NeuN protein, mouse; nuclear protein; animal; anxiety; biosynthesis; cognitive defect; disease model; epilepsy; genetics; hippocampus; human; knockout mouse; metabolism; mouse; pathology; pathophysiology; synaptic transmission; Animals; Anxiety; Cognition Disorders; Cytoskeletal Proteins; Disease Models, Animal; Early Growth Response Transcription Factors; Epilepsy; Hippocampus; Humans; Mice; Mice, Knockout; Nerve Tissue Proteins; Nuclear Proteins; Synaptic Transmission
Publisher
Nature Publishing Group
Type
journal article