The contribution of somatostatin(SOM)-expressing interneurons to the PTEN model of autism spectrum disorder

Tim Holford1, McLean Bolton1


Autism spectrum disorder (ASD) is a complex group of disorders with a large variability and despite the recent increase in diagnoses, scientists have advanced considerably less in their understanding of the mechanisms of ASD.  This may be due, in part, to the fact that no individual gene implicated in ASD is mutated in more than ~1% of patients.  PTEN is a regulator of gene expression, cell proliferation, and cell death via the mTOR signaling pathway and is a promising candidate gene for ASD because ~50% of patients with a PTEN mutation also test on the autism spectrum.  Additionally, many disorders have differences in the type and severity of symptoms, which makes it  difficult to identify an underlying endophenotype.  However, one proposed mechanism is that dysfunction of GABAergic interneurons may play a role in the development and progression of the disorder by interrupting the inhibitory balance of neural networks.  In our research, we elucidate the role of interneurons in ASD by selectively knocking out PTEN in somatostatin(SOM)- expressing interneurons.