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Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-/-) mice.


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(-/-)) 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.

SUBMITTER: Peixoto RT 

PROVIDER: S-EPMC4846490 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-/-) mice.

Peixoto Rui T RT   Wang Wengang W   Croney Donyell M DM   Kozorovitskiy Yevgenia Y   Sabatini Bernardo L BL  

Nature neuroscience 20160229 5


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 in  ...[more]

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