Xingzhi He1,2 • Yang Wang1,2 • Guangjun Zhou1,2 • Jing Yang1,2 • Jiarui Li1,2 • Tao Li1,2 • Hailan Hu1,2,3 • Huan Ma1,2,3

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

 

Abstract

    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, cCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons (LTPE?I). However, the molecular mechanism underlying how cCaMKII mediates LTPE?I remains unclear. Here, we show that cCaMKII 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, cCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95. Knocking down cCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors (AMPARs) in putative inhibitory interneurons, which are restored by overexpression of cCaMKII but not its kinase-dead form. Taken together, these data suggest that cCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.

 

 

Keywords

    Synaptic plasticity; LTP; Inhibitory interneurons; γCaMKII; AMPAR; NMDAR

 

 

[SpringerLink]