Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory
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 enh...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/164080 |
| _version_ | 1824455365879660544 |
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| author | 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 |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) 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 |
| author_sort | Zhai, Jing |
| collection | NTU |
| description | 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. |
| first_indexed | 2025-02-19T03:37:03Z |
| format | Journal Article |
| id | ntu-10356/164080 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:37:03Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1640802023-03-05T16:53:50Z Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory 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 Lee Kong Chian School of Medicine (LKCMedicine) National University of Singapore Science::Biological sciences RNA Editing Hippocampal Plasticity 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. Published version 2023-01-04T04:44:35Z 2023-01-04T04:44:35Z 2022 Journal Article 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-. https://dx.doi.org/10.1073/pnas.2203883119 0027-8424 https://hdl.handle.net/10356/164080 10.1073/pnas.2203883119 35914168 2-s2.0-85135355519 32 119 e2203883119 en Proceedings of the National Academy of Sciences of the United States of America © 2022 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). application/pdf |
| spellingShingle | Science::Biological sciences RNA Editing Hippocampal Plasticity 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 Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory |
| title | Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory |
| title_full | Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory |
| title_fullStr | Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory |
| title_full_unstemmed | Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory |
| title_short | Loss of Caᵥ1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory |
| title_sort | loss of caᵥ1 3 rna editing enhances mouse hippocampal plasticity learning and memory |
| topic | Science::Biological sciences RNA Editing Hippocampal Plasticity |
| url | https://hdl.handle.net/10356/164080 |
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