Inhibitory interneurons mediate autism-associated behaviors via 4E-BP2

Significance Disrupting cellular mechanisms that control protein synthesis can lead to autism spectrum disorder (ASD) in humans. Repetitive motions, impaired social interaction, and altered vocal communication are core symptoms of ASD and can be mimicked in mice. Deletion of the protein synthesis inhibitor, eukaryotic initiation factor 4E binding protein 2 (4E-BP2), causes autistic behaviors in mice. Using a variety of conditional knockout mouse models, we found that loss of 4E-BP2 in inhibitory neurons in the brain, but not in excitatory neurons or astrocytes, causes autistic behaviors.