Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation

Ammar H. Hawasli, David R. Benavides, Chan Nguyen, Janice W. Kansy, Kanehiro Hayashi, Pierre Chambon, Paul Greengard, Craig M. Powell, Donald C. Cooper, James A. Bibb

研究成果: Article査読

247 被引用数 (Scopus)

抄録

Learning is accompanied by modulation of postsynaptic signal transduction pathways in neurons. Although the neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) has been implicated in cognitive disorders, its role in learning has been obscured by the perinatal lethality of constitutive knockout mice. Here we report that conditional knockout of Cdk5 in the adult mouse brain improved performance in spatial learning tasks and enhanced hippocampal long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents. Enhanced synaptic plasticity in Cdk5 knockout mice was attributed to reduced NR2B degradation, which caused elevations in total, surface and synaptic NR2B subunit levels and current through NR2B-containing NMDARs. Cdk5 facilitated the degradation of NR2B by directly interacting with both it and its protease, calpain. These findings reveal a previously unknown mechanism by which Cdk5 facilitates calpain-mediated proteolysis of NR2B and may control synaptic plasticity and learning.

本文言語English
ページ(範囲)880-886
ページ数7
ジャーナルNature Neuroscience
10
7
DOI
出版ステータスPublished - 2007 7月 8
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)

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