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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.

Author information

1
Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal University, Shanghai 200062, China.
2
"Sagol" Department of Neurobiology, University of Haifa, Haifa 31905, Israel.
3
Department of Chinese Internal Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
4
Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal University, Shanghai 200062, China. Electronic address: xhcao@brain.ecnu.edu.cn.

Abstract

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.

KEYWORDS:

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

PMID:
28890075
DOI:
10.1016/j.expneurol.2017.09.004
[Indexed for MEDLINE]

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