دورية أكاديمية
BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination
| العنوان: | BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination |
|---|---|
| المؤلفون: | 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 |
| المساهمون: | National Natural Science Foundation of China |
| المصدر: | Signal Transduction and Targeted Therapy ; volume 7, issue 1 ; ISSN 2059-3635 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Genetics |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41392-022-00989-x |
| الإتاحة: | https://doi.org/10.1038/s41392-022-00989-xTest https://www.nature.com/articles/s41392-022-00989-x.pdfTest https://www.nature.com/articles/s41392-022-00989-xTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.F63FC6DE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41392-022-00989-x |
|---|