Program in Neuroscience, Hussman Institute for Autism, Baltimore, MD, 21201, USA.
Mol Brain. 2021 Jan 27;14(1):24. doi: 10.1186/s13041-021-00731-8.
Disrupted GABAergic neurons have been extensively described in brain tissues from individuals with autism spectrum disorder (ASD) and animal models for ASD. However, the contribution of these aberrant inhibitory neurons to autism-related behavioral phenotypes is not well understood. We examined ASD-related behaviors in mice with conditional Pten knockout in parvalbumin (PV)-expressing or somatostatin (Sst)-expressing neurons, two common subtypes of GABAergic 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 and home cages. 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.
在自闭症谱系障碍 (ASD) 患者的脑组织和 ASD 动物模型中，广泛描述了 GABA 能神经元的紊乱。然而，这些异常抑制性神经元对自闭症相关行为表型的贡献尚不清楚。我们研究了条件性 Pten 敲除在表达 Parvalbumin (PV)或表达 Somatostatin (Sst)的神经元中的 ASD 相关行为，这两种神经元是 GABA 能神经元的两种常见亚型。我们发现，PV 神经元或 Sst 神经元中 Pten 缺失的小鼠表现出社交缺陷、重复行为和运动协调/学习障碍。此外，PV 神经元中 Pten 缺失一个拷贝的小鼠在新的开放场和家笼中表现出过度活动。我们还检查了焦虑行为，发现 Sst 神经元中 Pten 缺失的小鼠表现出类似焦虑的行为，而 PV 神经元中 Pten 缺失的小鼠则表现出类似焦虑的行为。这些行为评估表明，抑制性神经元亚型中的 Pten 敲除足以引起 ASD 的核心行为，这为 PV 和 Sst 神经元可能在 ASD 症状中发挥关键作用提供了证据。
