Identification and characterization of long non-coding RNA Carip in modulating spatial learning and memory
Xiaoli Cui, Ruijin Zhang, Ye Yang, Erzhong Wu, Yiheng Tang, Zhihua Zhao, Chao Li, Lei Yang, Xueyi Teng, Yanzhen Ye, Ya Cui, Feng Xu, Zewen Su, Dongpeng Wang, Dongdong Zhang, Yanhui Yang, Jianyuan Sun, Jianjun Luo, Shuli Zhang, Runsheng Chen, Jianzhong Xi
Abstract
CaMKII has long been known to be a key effector for synaptic plasticity. Recent studies have shown that a variety of modulators interact with the subunits of CaMKII to regulate the long-term potentiation (LTP) of hippocampal neurons. However, whether long non-coding RNAs modulate the activity of CaMKII and affect synaptic plasticity is still elusive. Here, we identify a previously uncharacterized long non-coding RNA Carip that functions as a scaffold, specifically interacts with CaMKIIβ, and regulates the phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor subunits in the hippocampus. The absence of Carip causes dysfunction of synaptic transmission and attenuates LTP in hippocampal CA3-CA1 synapses, which further leads to impairment of spatial learning and memory. In summary, our findings demonstrate that Carip modulates long-term synaptic plasticity by changing AMPA receptor and NMDA receptor activities, thereby affecting spatial learning and memory in mice.