Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory

• Main Authors: Zhai, Jing, Navakkode, Sheeja, Yeow, Sean Qing Zhang, Krishna-K, Kumar, Liang, Mui Cheng, Koh, Joanne Huifen, Wong, Rui Xiong, Yu, Wei Ping, Sajikumar, Sreedharan, Huang, Hua, Soong, Tuck Wah
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; RNA Editing; Hippocampal Plasticity
• Online Access: https://hdl.handle.net/10356/164080
• Institution: Nanyang Technological University

L-type CaV1.3 calcium channels are expressed on the dendrites and soma of neurons, and there is a paucity of information about its role in hippocampal plasticity. Here, by genetic targeting to ablate CaV1.3 RNA editing, we demonstrate that unedited CaV1.3ΔECS mice exhibited improved learning and enhanced long-term memory, supporting a functional role of RNA editing in behavior. Significantly, the editing paradox that functional recoding of CaV1.3 RNA editing sites slows Ca2+-dependent inactivation to increase Ca2+ influx but reduces channel open probability to decrease Ca2+ influx was resolved. Mechanistically, using hippocampal slice recordings, we provide evidence that unedited CaV1.3 channels permitted larger Ca2+ influx into the hippocampal pyramidal neurons to bolster neuronal excitability, synaptic transmission, late long-term potentiation, and increased dendritic arborization. Of note, RNA editing of the CaV1.3 IQ-domain was found to be evolutionarily conserved in mammals, which lends support to the importance of the functional recoding of the CaV1.3 channel in brain function.