Cortical interneurons in autism

This Review discusses evidence from human studies and mouse models that cortical interneurons are involved in the pathophysiology of autism and that parvalbumin cell hypofunction may be a primary driver of circuit dysfunction in autism. The mechanistic underpinnings of autism remain a subject of debate and controversy. Why do individuals with autism share an overlapping set of atypical behaviors and symptoms, despite having different genetic and environmental risk factors? A major challenge in developing new therapies for autism has been the inability to identify convergent neural phenotypes that could explain the common set of symptoms that result in the diagnosis. Although no striking macroscopic neuropathological changes have been identified in autism, there is growing evidence that inhibitory interneurons (INs) play an important role in its neural basis. In this Review, we evaluate and interpret this evidence, focusing on recent findings showing reduced density and activity of the parvalbumin class of INs. We discuss the need for additional studies that investigate how genes and the environment interact to change the developmental trajectory of INs, permanently altering their numbers, connectivity and circuit engagement.

Automated summary

The pathophysiology of autism remains controversial, with evidence suggesting that dysfunction of cortical interneurons may play a significant role. In particular, reduced density and activity of parvalbumin interneurons have been implicated in autism spectrum disorders. Further research into the interaction of genes and the environment on the development of interneurons is needed to better understand the neural basis of autism.