A Critical Role for γCaMKII in Decoding NMDA Signaling to Regulate AMPA Receptors in Putative Inhibitory Interneurons  

作　　者：Xingzhi He Yang Wang Guangjun Zhou Jing Yang Jiarui Li Tao Li Hailan Hu Huan Ma 

机构地区：[1]Department of Neurobiology,Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital,Zhejiang University School of Medicine,Hangzhou,310058,China [2]NHC and CAMS Key Laboratory of Medical Neurobiology,MOE Frontier Science Center for Brain Research and Brain–Machine Integration,School of Brain Science and Brain Medicine,Zhejiang University,Hangzhou,310058,China [3]Research Units for Emotion and Emotion disorders,Chinese Academy of Medical Sciences,Beijing,100730,China

出　　处：《Neuroscience Bulletin》2022年第8期916-926,共11页神经科学通报（英文版）

基　　金：This work was supported by Science and Technology Innovation 2030-Major Project(2021ZD0203501);the National Natural Science Foundation of China(81930030,31771109,and 31722023);the National Key R&D Program of China(2019YFA0508603);CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057);Project for Hangzhou Medical Disciplines of Excellence;Key Project for Hangzhou Medical Disciplines;the Fundamental Research Funds for the Central Universities of China(2018XZZX002-02,2019XZZX001-01-04,and 2019FZA7009);the National Postdoctoral Program for Innovative Talents(BX2021263).

摘　　要：CaMKII is essential for long-term potentiation(LTP),a process in which synaptic strength is increased following the acquisition of information.Among the four CaMKII isoforms,γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons(LTPE→I).However,the molecular mechanism underlying howγCaMKII mediates LTPE→I remains unclear.Here,we show thatγCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10–30 Hz range.Following stimulation,γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95.Knocking downγCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors(AMPARs)in putative inhibitory interneurons,which are restored by overexpression ofγCaMKII but not its kinase-dead form.Taken together,these data suggest thatγCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.

关 键 词：Synaptic plasticity LTP Inhibitory interneurons γCaMKII AMPAR NMDAR 

分 类 号：R114[医药卫生—卫生毒理学]