Disrupted interneurons have been extensively described in brain tissues from individuals with autism spectrum disorder (ASD) and animal models for ASD. However, the contribution of aberrant interneurons to autism-related behavioral phenotypes is not well understood. We examined ASD-related behaviors in mice with conditional Pten knockout in parvalbumin (PV)-expressing and somatostatin (Sst)-expressing neurons, two prominent subtypes of inhibitory neurons. We found that mice with deletion of Pten in either PV-neurons or Sst-neurons displayed social deficits, repetitive behaviors and impaired motor coordination/learning. In addition, mice with one copy of Pten deletion in PV-neurons exhibited hyperlocomotion in novel open fields. We also examined anxiety behaviors and found that mice with Pten deletion in Sst-neurons displayed anxiety-like behaviors, while mice with Pten deletion in PV-neurons exhibited anxiolytic-like behaviors. These behavioral assessments demonstrate that Pten knockout in the subtype of inhibitory neurons sufficiently gives rise to ASD-core behaviors, providing evidence that both PV- and Sst-neurons may play a critical role in ASD symptoms.### Competing Interest StatementThe authors have declared no competing interest.

Conditional Pten knockout in parvalbumin- or somatostatin-positive neurons sufficiently leads to autism-related behavioral phenotypes