BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination

Xiu Xiu Liu, Xing Hui Chen, Zhi Wei Zheng, Qin Jiang, Chen Li, Lin Yang, Xiang Chen, Xing Feng Mao, Hao Yang Yuan, Li Li Feng, Quan Jiang, Wei Xing Shi, Takuya Sasaki, Kohji Fukunaga, Zhong Chen, Feng Han, Ying Mei Lu

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1 Citation (Scopus)


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.

Original languageEnglish
Article number170
JournalSignal Transduction and Targeted Therapy
Issue number1
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • Genetics
  • Cancer Research


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