| First Author | Chang HHV | Year | 2022 |
| Journal | Cells | Volume | 11 |
| Issue | 17 | PubMed ID | 36078147 |
| Mgi Jnum | J:329002 | Mgi Id | MGI:7339554 |
| Doi | 10.3390/cells11172739 | Citation | Chang HHV, et al. (2022) Loss of Flocculus Purkinje Cell Firing Precision Leads to Impaired Gaze Stabilization in a Mouse Model of Spinocerebellar Ataxia Type 6 (SCA6). Cells 11(17) |
| abstractText | Spinocerebellar Ataxia Type 6 (SCA6) is a mid-life onset neurodegenerative disease characterized by progressive ataxia, dysarthria, and eye movement impairment. This autosomal dominant disease is caused by the expansion of a CAG repeat tract in the CACNA1A gene that encodes the alpha1A subunit of the P/Q type voltage-gated Ca(2+) channel. Mouse models of SCA6 demonstrate impaired locomotive function and reduced firing precision of cerebellar Purkinje in the anterior vermis. Here, to further assess deficits in other cerebellar-dependent behaviors, we characterized the oculomotor phenotype of a knock-in mouse model with hyper-expanded polyQ repeats (SCA6(84Q)). We found a reduction in the efficacy of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) in SCA6 mutant mice, without a change in phase, compared to their litter-matched controls. Additionally, VOR motor learning was significantly impaired in SCA6(84Q) mice. Given that the floccular lobe of the cerebellum plays a vital role in the generation of OKR and VOR calibration and motor learning, we investigated the firing behavior and morphology of floccular cerebellar Purkinje cells. Overall, we found a reduction in the firing precision of floccular lobe Purkinje cells but no morphological difference between SCA6(84Q) and wild-type mice. Taken together, our findings establish that gaze stabilization and motor learning are impaired in SCA6(84Q) mice and suggest that altered cerebellar output contributes to these deficits. |
