Volume 7 Issue 7, Jul 2022:
Article
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
ORCID: orcid.org/0000-0002-4059-3184,Li-Li Feng,Quan Jiang,Wei-Xing Shi,Takuya Sasaki,Kohji Fukunaga,Zhong Chen
ORCID: orcid.org/0000-0003-4755-9357,Feng Han &…Ying-Mei Lu
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.
