摘要：SummaryImpairments in synapse development are thought to cause numerous psychiatric disorders.Autism susceptibility candidate 2(AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in theAuts2-deficient primary cultured neurons as well asAuts2mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression inAuts2mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability.Auts2mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals withAUTS2mutations.Graphical AbstractDisplay OmittedHighlights•AUTS2 regulates excitatory synapse number in forebrain pyramidal neurons•Loss ofAuts2leads to increased spine formation in development and adulthood•Loss ofAuts2alters the balance of excitatory and inhibitory synaptic inputs•Auts2mutant mice exhibit cognitive and sociobehavioral deficitsNeuroscience; Behavioral Neuroscience; Molecular Neuroscience; Transcriptomics
