| Autor: |
Rui Tiago Peixoto, Lynne Chantranupong, Richard Hakim, James Levasseur, Wengang Wang, Tasha Merchant, Kelly Gorman, Bogdan Budnik, Bernardo Luis Sabatini |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 29, Iss 7, Pp 2016-2027.e4 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.10.021 |
| Popis: |
Summary: The neural substrates and pathophysiological mechanisms underlying the onset of cognitive and motor deficits in autism spectrum disorders (ASDs) remain unclear. Mutations in ASD-associated SHANK3 in mice (Shank3B−/−) result in the accelerated maturation of corticostriatal circuits during the second and third postnatal weeks. Here, we show that during this period, there is extensive remodeling of the striatal synaptic proteome and a developmental switch in glutamatergic synaptic plasticity induced by cortical hyperactivity in striatal spiny projection neurons (SPNs). Behavioral abnormalities in Shank3B−/− mice emerge during this stage and are ameliorated by normalizing excitatory synapse connectivity in medial striatal regions by the downregulation of PKA activity. These results suggest that the abnormal postnatal development of striatal circuits is implicated in the onset of behavioral deficits in Shank3B−/− mice and that modulation of postsynaptic PKA activity can be used to regulate corticostriatal drive in developing SPNs of mouse models of ASDs and other neurodevelopmental disorders. : Peixoto et al. show that the onset of behavioral deficits in Shank3B−/− mice occurs during early postnatal development and that these can be ameliorated by reducing the glutamatergic synaptic drive in medial regions of the striatum by the downregulation of PKA activity. Keywords: corticostriatal, development, striatal, cortical, autism, Shank3, ASD, synaptic, plasticity, circuit |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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