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

Abstract

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.