| First Author | Peixoto RT | Year | 2016 |
| Journal | Nat Neurosci | Volume | 19 |
| Issue | 5 | Pages | 716-24 |
| PubMed ID | 26928064 | Mgi Jnum | J:234566 |
| Mgi Id | MGI:5790274 | Doi | 10.1038/nn.4260 |
| Citation | Peixoto RT, et al. (2016) Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-/-) mice. Nat Neurosci 19(5):716-24 |
| abstractText | 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 that is 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(-/-)) shows early cortical hyperactivity, which triggers increased SPN excitatory synapse and corticostriatal hyperconnectivity. These results indicate that there is a tight functional coupling between cortex and striatum during early postnatal development and suggest a potential common circuit dysfunction that is caused by cortical hyperactivity. |
