摘要：SummaryThe transcription factor Aristaless-related X-linked gene (Arx) is a monogenic factor in early onset epileptic encephalopathies (EOEEs) and a fundamental regulator of early stages of brain development. However,Arxexpression persists in mature GABAergic neurons with an unknown role. To address this issue, we generated a conditional knockout (CKO) mouse in which postnatalArxwas ablated in parvalbumin interneurons (PVIs). Electroencephalogram (EEG) recordings in CKO mice revealed an increase in theta oscillations and the occurrence of occasional seizures. Behavioral analysis uncovered an increase in anxiety. Genome-wide sequencing of fluorescence activated cell sorted (FACS) PVIs revealed thatArximpinged on network excitability via genes primarily associated with synaptic and extracellular matrix pathways. Whole-cell recordings revealed prominent hypoexcitability of various intrinsic and synaptic properties. These results revealed important roles for postnatalArxexpression in PVIs in the control of neural circuits and that dysfunction in those roles alone can cause EOEE-like network abnormalities.Graphical AbstractDisplay OmittedHighlights•ArxCKO mice displayed abnormal theta rhythms, occasional seizures, and anxiety•Loss ofArxin PV interneurons broadly altered their gene expression profiles•The perineuronal net around PV interneurons was altered inArxCKO mice•Loss ofArxin PV interneurons altered their intrinsic and synaptic propertiesBehavioral Neuroscience ; Molecular Neuroscience; Cellular Neuroscience; Transcriptomics
