Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B â '/â ' mice

Rui T. Peixoto, Wengang Wang, Donyell M. Croney, Yevgenia Kozorovitskiy, Bernardo L. Sabatini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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 â '/â ') 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.

Original languageEnglish (US)
Pages (from-to)716-724
Number of pages9
JournalNature Neuroscience
Volume19
Issue number5
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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