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Exp Neurol. 2017 Dec;298(Pt A):112-121. doi: 10.1016/j.expneurol.2017.09.004. Epub 2017 Sep 8.

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

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Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal University, Shanghai 200062, China.
"Sagol" Department of Neurobiology, University of Haifa, Haifa 31905, Israel.
Department of Chinese Internal Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal University, Shanghai 200062, China. Electronic address:


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.


AMPAR; Long term potentiation; NMDAR; Neural disorders; Striatum; αCaMKII

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