Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction
Drebrin is an actin-binding protein that is preferentially expressed in the brain. It is highly localized in dendritic spines and regulates spine shapes. The embryonic-type (drebrin E) is expressed in the embryonic and early postnatal brain and is replaced by the adult-type (drebrin A) during develo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00330/full |
| _version_ | 1818927822291337216 |
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| author | Hiroki Yasuda Hiroki Yasuda Hiroki Yasuda Nobuhiko Kojima Nobuhiko Kojima Kenji Hanamura Hiroyuki Yamazaki Kenji Sakimura Tomoaki Shirao Tomoaki Shirao |
| author_facet | Hiroki Yasuda Hiroki Yasuda Hiroki Yasuda Nobuhiko Kojima Nobuhiko Kojima Kenji Hanamura Hiroyuki Yamazaki Kenji Sakimura Tomoaki Shirao Tomoaki Shirao |
| author_sort | Hiroki Yasuda |
| collection | DOAJ |
| description | Drebrin is an actin-binding protein that is preferentially expressed in the brain. It is highly localized in dendritic spines and regulates spine shapes. The embryonic-type (drebrin E) is expressed in the embryonic and early postnatal brain and is replaced by the adult-type (drebrin A) during development. In parallel, NMDA receptor (NMDAR)-dependent long-term depression (LTD) of synaptic transmission, induced by low-frequency stimulation (LFS), is dominant in the immature brain and decreases during development. Here, we report that drebrin regulates NMDAR-dependent and group 1 metabotropic glutamate receptor (mGluR)-dependent LTD induction in the hippocampus. While LFS induced NMDAR-dependent LTD in the developing hippocampus in wild-type (WT) mice, it did not induce LTD in developing drebrin E and A double knockout (DXKO) mice, indicating that drebrin is required for NMDAR-dependent LTD. On the other hand, LFS induced robust LTD dependent on mGluR5, one of group 1 mGluRs, in both developing and adult brains of drebrin A knockout (DAKO) mice, in which drebrin E is expressed throughout development and adulthood. Agonist-induced mGluR-dependent LTD was normal in WT and DXKO mice; however, it was enhanced in DAKO mice. Also, mGluR1, another group 1 mGluR, was involved in agonist-induced mGluR-dependent LTD in DAKO mice. These data suggest that abnormal drebrin E expression in adults promotes group 1 mGluR-dependent LTD induction. Therefore, while drebrin expression is critical for NMDAR-dependent LTD induction, developmental conversion from drebrin E to drebrin A prevents robust group 1 mGluR-dependent LTD. |
| first_indexed | 2024-12-20T03:19:07Z |
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| id | doaj.art-af81f4fc9e874d1f8722d71a0c740a2f |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-20T03:19:07Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-af81f4fc9e874d1f8722d71a0c740a2f2022-12-21T19:55:16ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-10-011210.3389/fncel.2018.00330357432Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD InductionHiroki Yasuda0Hiroki Yasuda1Hiroki Yasuda2Nobuhiko Kojima3Nobuhiko Kojima4Kenji Hanamura5Hiroyuki Yamazaki6Kenji Sakimura7Tomoaki Shirao8Tomoaki Shirao9Department of Neurobiology and Behavior, Graduate School of Medicine, Gunma University, Maebashi, JapanEducation and Research Support Center, Graduate School of Medicine, Gunma University, Maebashi, JapanDivision of Physiology, Faculty of Medicine, Saga University, Saga, JapanDepartment of Neurobiology and Behavior, Graduate School of Medicine, Gunma University, Maebashi, JapanFaculty of Life Sciences, Toyo University, Itakura, JapanDepartment of Neurobiology and Behavior, Graduate School of Medicine, Gunma University, Maebashi, JapanDepartment of Neurobiology and Behavior, Graduate School of Medicine, Gunma University, Maebashi, JapanDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Neurobiology and Behavior, Graduate School of Medicine, Gunma University, Maebashi, JapanEducation and Research Support Center, Graduate School of Medicine, Gunma University, Maebashi, JapanDrebrin is an actin-binding protein that is preferentially expressed in the brain. It is highly localized in dendritic spines and regulates spine shapes. The embryonic-type (drebrin E) is expressed in the embryonic and early postnatal brain and is replaced by the adult-type (drebrin A) during development. In parallel, NMDA receptor (NMDAR)-dependent long-term depression (LTD) of synaptic transmission, induced by low-frequency stimulation (LFS), is dominant in the immature brain and decreases during development. Here, we report that drebrin regulates NMDAR-dependent and group 1 metabotropic glutamate receptor (mGluR)-dependent LTD induction in the hippocampus. While LFS induced NMDAR-dependent LTD in the developing hippocampus in wild-type (WT) mice, it did not induce LTD in developing drebrin E and A double knockout (DXKO) mice, indicating that drebrin is required for NMDAR-dependent LTD. On the other hand, LFS induced robust LTD dependent on mGluR5, one of group 1 mGluRs, in both developing and adult brains of drebrin A knockout (DAKO) mice, in which drebrin E is expressed throughout development and adulthood. Agonist-induced mGluR-dependent LTD was normal in WT and DXKO mice; however, it was enhanced in DAKO mice. Also, mGluR1, another group 1 mGluR, was involved in agonist-induced mGluR-dependent LTD in DAKO mice. These data suggest that abnormal drebrin E expression in adults promotes group 1 mGluR-dependent LTD induction. Therefore, while drebrin expression is critical for NMDAR-dependent LTD induction, developmental conversion from drebrin E to drebrin A prevents robust group 1 mGluR-dependent LTD.https://www.frontiersin.org/article/10.3389/fncel.2018.00330/fulldrebrin isoformsNMDAR-dependent LTDmGluR-dependent LTDknockout mousedevelopment |
| spellingShingle | Hiroki Yasuda Hiroki Yasuda Hiroki Yasuda Nobuhiko Kojima Nobuhiko Kojima Kenji Hanamura Hiroyuki Yamazaki Kenji Sakimura Tomoaki Shirao Tomoaki Shirao Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction Frontiers in Cellular Neuroscience drebrin isoforms NMDAR-dependent LTD mGluR-dependent LTD knockout mouse development |
| title | Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction |
| title_full | Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction |
| title_fullStr | Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction |
| title_full_unstemmed | Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction |
| title_short | Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction |
| title_sort | drebrin isoforms critically regulate nmdar and mglur dependent ltd induction |
| topic | drebrin isoforms NMDAR-dependent LTD mGluR-dependent LTD knockout mouse development |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00330/full |
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