iScience
Volume 23, Issue 6, 26 June 2020, 101183
Journal home page for iScience

Article
AUTS2 Regulation of Synapses for Proper Synaptic Inputs and Social Communication

https://doi.org/10.1016/j.isci.2020.101183Get rights and content
Under a Creative Commons license
open access

Highlights

  • AUTS2 regulates excitatory synapse number in forebrain pyramidal neurons

  • Loss of Auts2 leads to increased spine formation in development and adulthood

  • Loss of Auts2 alters the balance of excitatory and inhibitory synaptic inputs

  • Auts2 mutant mice exhibit cognitive and sociobehavioral deficits

Summary

Impairments 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 the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant 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 with AUTS2 mutations.

Subject Areas

Neuroscience
Behavioral Neuroscience
Molecular Neuroscience
Transcriptomics

Cited by (0)

12

Present address: Department of Animal Model development, Brain Research Institute, Niigata University, Niigata 951-8585, Japan

13

Lead Contact