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BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination
Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156688/ https://www.ncbi.nlm.nih.gov/pubmed/35641478 http://dx.doi.org/10.1038/s41392-022-00989-x |
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author | Liu, Xiu-Xiu Chen, Xing-Hui Zheng, Zhi-Wei Jiang, Qin Li, Chen Yang, Lin Chen, Xiang Mao, Xing-Feng Yuan, Hao-Yang Feng, Li-Li Jiang, Quan Shi, Wei-Xing Sasaki, Takuya Fukunaga, Kohji Chen, Zhong Han, Feng Lu, Ying-Mei |
author_facet | Liu, Xiu-Xiu Chen, Xing-Hui Zheng, Zhi-Wei Jiang, Qin Li, Chen Yang, Lin Chen, Xiang Mao, Xing-Feng Yuan, Hao-Yang Feng, Li-Li Jiang, Quan Shi, Wei-Xing Sasaki, Takuya Fukunaga, Kohji Chen, Zhong Han, Feng Lu, Ying-Mei |
author_sort | Liu, Xiu-Xiu |
collection | PubMed |
description | Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIα(+) neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα(+) neurons in the FN and ameliorated ataxia behaviors in L7-Cre; BOD1(f/f) mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobe(PCs )→ FN(CaMKIIα+) circuit might provide neuromodulatory targets for the treatment of ataxia behaviors. |
format | Online Article Text |
id | pubmed-9156688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91566882022-06-02 BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination Liu, Xiu-Xiu Chen, Xing-Hui Zheng, Zhi-Wei Jiang, Qin Li, Chen Yang, Lin Chen, Xiang Mao, Xing-Feng Yuan, Hao-Yang Feng, Li-Li Jiang, Quan Shi, Wei-Xing Sasaki, Takuya Fukunaga, Kohji Chen, Zhong Han, Feng Lu, Ying-Mei Signal Transduct Target Ther Article Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIα(+) neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα(+) neurons in the FN and ameliorated ataxia behaviors in L7-Cre; BOD1(f/f) mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobe(PCs )→ FN(CaMKIIα+) circuit might provide neuromodulatory targets for the treatment of ataxia behaviors. Nature Publishing Group UK 2022-06-01 /pmc/articles/PMC9156688/ /pubmed/35641478 http://dx.doi.org/10.1038/s41392-022-00989-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Liu, Xiu-Xiu Chen, Xing-Hui Zheng, Zhi-Wei Jiang, Qin Li, Chen Yang, Lin Chen, Xiang Mao, Xing-Feng Yuan, Hao-Yang Feng, Li-Li Jiang, Quan Shi, Wei-Xing Sasaki, Takuya Fukunaga, Kohji Chen, Zhong Han, Feng Lu, Ying-Mei BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination |
title | BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination |
title_full | BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination |
title_fullStr | BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination |
title_full_unstemmed | BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination |
title_short | BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination |
title_sort | bod1 regulates the cerebellar iv/v lobe-fastigial nucleus circuit associated with motor coordination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156688/ https://www.ncbi.nlm.nih.gov/pubmed/35641478 http://dx.doi.org/10.1038/s41392-022-00989-x |
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