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

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

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Title: Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B−/− mice
Author: Peixoto, Rui T.; Wang, Wengang; Croney, Donyell M.; Kozorovitskiy, Yevgenia; Sabatini, Bernardo L.

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Citation: Peixoto, Rui T., Wengang Wang, Donyell M. Croney, Yevgenia Kozorovitskiy, and Bernardo L. Sabatini. 2016. “Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B−/− mice.” Nature neuroscience 19 (5): 716-724. doi:10.1038/nn.4260. http://dx.doi.org/10.1038/nn.4260.
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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 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.
Published Version: doi:10.1038/nn.4260
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846490/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002590
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