Down-regulation of dorsal striatal αCaMKII causes striatum-related cognitive and synaptic disorders

Qi Wang, Pengcheng Yin, Bin Yu, Zheng Zhao, Gal Richter-Levin, Lu Yu, Xiaohua Cao

Research output: Contribution to journalArticlepeer-review


Alpha calcium/calmodulin dependent protein kinase II (αCaMKII) is a serine/threonine protein kinase which is expressed abundantly in dorsal striatum and is highly involved in the corticostriatal synaptic plasticity. Nevertheless, it currently remains unclear whether and how αCaMKII plays a in the striatum-related neural disorders. To address the above issue, lentivirus-mediated short hairpin RNA (shRNA) was used to silence the expression of αCaMKII gene in the dorsal striatum of mice. As a consequence of down-regulation of dorsal striatal αCaMKII expression, we observed defective motor skill learning in accelerating rotarod and response learning in water cross maze. Furthermore, impaired corticostriatal basal transmission and long-term potentiation (LTP), which correlated with the deficits in dorsal striatum-related cognition, were also detected in the αCaMKII-shRNA mice. Consistent with the above results, αCaMKII-shRNA mice exhibited a remarkable decline in GluA1-Ser831 and GluA1-Ser845 phosphorylation levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and a decline in the expression levels of N-methyl-D-aspartic acid receptor (NMDAR) subunits NR1, NR2A and NR2B. Taken together, αCaMKII down-regulation caused dorsal striatum-related cognitive disorders by inhibiting corticostriatal synaptic plasticity, which resulted from dysfunction of AMPARs and NMDARs. Our findings demonstrate for the first time an important role of αCaMKII in striatum-related neural disorders and provide further evidence for the proposition that corticostriatal LTP underlies aspects of dorsal striatum-related cognition.

Original languageEnglish
Pages (from-to)112-121
Number of pages10
JournalExperimental Neurology
StatePublished - Dec 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.


  • Long term potentiation
  • Neural disorders
  • Striatum
  • αCaMKII

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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