Some autistic individuals exhibit abnormal development of the caudate nucleus and associative cortical areas, suggesting potential dysfunction of cortico-basal ganglia (BG) circuits. Using optogenetic and electrophysiological approaches in mice we identified a narrow postnatal period characterized by extensive glutamatergic synaptogenesis in striatal spiny projection neurons (SPNs) and a concomitant increase in corticostriatal circuit activity. SPNs during early development have high intrinsic excitability and respond strongly to cortical afferents despite sparse excitatory inputs. As a result, striatum and corticostriatal connectivity are highly sensitive to acute and chronic changes in cortical activity, suggesting that early imbalances in cortical function alter BG development. Indeed, a mouse model of autism with deletions in SHANK3 (Shank3B−/−) has early cortical hyperactivity, which triggers increased SPN excitatory synapse and corticostriatal hyper-connectivity. These results show a tight functional coupling between cortex and striatum during early postnatal development and suggest a potential common circuit dysfunction caused by cortical hyperactivity.
