UC San Diego

Alteration in ionotropic glutamatergic transmission onto developing inhibitory systems has been proposed as an underlying mechanism in the pathogenesis of several neurodevelopmental disorders, including schizophrenia and autism. In particular, accumulating evidence shows that alteration in the development of parvalbumin-positive (Pv+ ) fast-spiking interneurons can produce long-term neurophysiological and behavioral disruptions. Here we show that separate postnatal ablations of the metabotropic glutamate receptor 5 (mGluR5) and the scaffolding protein Densin-180 (Densin) from Pv+ interneurons alter stimulus- evoked neuronal responses, oscillatory cortical dynamics and sensorimotor information processing. This implies that multiple alterations in the development of Pv+ neurons can produce both convergent and divergent neurophysiological and cognitive consequences. Together, these results suggest a fundamental role for mGluR5 and Densin in the development of Pv+ neurons, and provide a novel mechanism by which alterations in glutamatergic transmission onto this inhibitory circuitry can modify brain activity in ways that resemble specific features of neurodevelopmental disorders