{"doi":"10.3390/cells11172739","title":"Loss of Flocculus Purkinje Cell Firing Precision Leads to Impaired Gaze Stabilization in a Mouse Model of Spinocerebellar Ataxia Type 6 (SCA6)","abstract":"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 α1A subunit of the P/Q type voltage-gated Ca2+ 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 (SCA684Q). 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 SCA684Q 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 SCA684Q and wild-type mice. Taken together, our findings establish that gaze stabilization and motor learning are impaired in SCA684Q mice and suggest that altered cerebellar output contributes to these deficits.","journal":"Cells","year":2022,"id":262363,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":877201,"name":"Anna A. Cook","orcid":"0000-0001-7654-0212","position":1,"is_corresponding":false},{"id":877207,"name":"Alanna J. Watt","orcid":"0000-0002-6371-6220","position":2,"is_corresponding":false},{"id":279456,"name":"Kathleen E. Cullen","orcid":"0000-0002-9348-0933","position":3,"is_corresponding":false},{"id":279452,"name":"Hui Ho Vanessa Chang","orcid":"0009-0005-9924-6143","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T00:26:20.717229Z","pmid":"36078147","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}