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- Title
BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination.
- Authors
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
- Abstract
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; BOD1f/f mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobePCs → FNCaMKIIα+ circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.
- Publication
Signal Transduction & Targeted Therapy, 2022, Vol 7, Issue 1, p1
- ISSN
2095-9907
- Publication type
Article
- DOI
10.1038/s41392-022-00989-x