Journal
NATURE NEUROSCIENCE
Volume 19, Issue 5, Pages 716-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4260
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Funding
- Alice and Joseph Brooks fellowship
- Nancy Lurie Marks clinical and research fellowship in autism
- Leonard and Isabelle Goldenson Research Fellowship
- Nancy Lurie Marks Family Foundation
- National Institute of Neurological Disorders and Stroke [NS046579]
- Nancy Lurie Marks Foundation
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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.
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