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Title: Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory
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
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Zhai, J., Navakkode, S., Yeow, S. Q. Z., Krishna-K, K., Liang, M. C., Koh, J. H., Wong, R. X., Yu, W. P., Sajikumar, S., Huang, H. & Soong, T. W. (2022). Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory. Proceedings of the National Academy of Sciences of the United States of America, 119(32), e2203883119-.
Journal: Proceedings of the National Academy of Sciences of the United States of America 
Abstract: 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.
ISSN: 0027-8424
DOI: 10.1073/pnas.2203883119
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: National University of Singapore
Rights: © 2022 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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