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https://doi.org/10.1073/pnas.2203883119
Title: | Loss of CaV1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory | Authors: | Zhai, J Navakkode, S Yeow, SQZ Krishna-K, K Liang, MC Koh, JH Wong, RX Yu, WP Sajikumar, S Huang, H Soong, TW |
Keywords: | CaV1.3 calcium channel RNA editing hippocampal plasticity spatial learning and memory Animals Calcium Channels, L-Type Hippocampus Mammals Mice Neuronal Plasticity Neurons Pyramidal Cells RNA Editing |
Issue Date: | 9-Aug-2022 | Publisher: | Proceedings of the National Academy of Sciences | Citation: | Zhai, J, Navakkode, S, Yeow, SQZ, Krishna-K, K, Liang, MC, Koh, JH, Wong, RX, Yu, WP, Sajikumar, S, Huang, H, Soong, TW (2022-08-09). 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-. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.2203883119 | 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. | Source Title: | Proceedings of the National Academy of Sciences of the United States of America | URI: | https://scholarbank.nus.edu.sg/handle/10635/237737 | ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.2203883119 |
Appears in Collections: | Staff Publications Elements |
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