BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination.
Signal Transduct Target Ther
; 7(1): 170, 2022 06 01.
Article
em En
| MEDLINE
| ID: mdl-35641478
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 â FNCaMKIIα+ circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células de Purkinje
/
Núcleos Cerebelares
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article