{"doi":"10.17615/889z-hy49","title":"Genetic essential tremor in γ-aminobutyric acidA receptor α1 subunit knockout mice","abstract":"Essential tremor is the most common movement disorder and has an unknown etiology. Here we report that γ-aminobutyric acidA (GABAA) receptor α1–/– mice exhibit postural and kinetic tremor and motor incoordination that is characteristic of essential tremor disease. We tested mice with essential-like tremor using current drug therapies that alleviate symptoms in essential tremor patients (primidone, propranolol, and gabapentin) and several candidates hypothesized to reduce tremor, including ethanol; the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801; the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABAA receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ channel antagonist nitrendipine. Primidone, propranolol, and gabapentin reduced the amplitude (power) of the pathologic tremor. Nonsedative doses of ethanol eliminated tremor in mice. Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no effect or enhanced tremor, whereas MK-801 and CCPA reduced tremor. To understand the etiology of tremor in these mice, we studied the electrophysiological properties of cerebellar Purkinje cells. Cerebellar Purkinje cells in GABAA receptor α1–/– mice exhibited a profound loss of all responses to synaptic or exogenous GABA, but no differences in abundance, gross morphology, or spontaneous synaptic activity were observed. This genetic animal model elucidates a mechanism of GABAergic dysfunction in the major motor pathway and potential targets for pharmacotherapy of essential tremor.","journal":"UNC Libraries","year":2020,"id":144173,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":612680,"name":"Douglas B. Matthews","orcid":"0000-0002-6518-4280","position":1,"is_corresponding":false},{"id":613101,"name":"Jason E. Kralic","orcid":null,"position":2,"is_corresponding":false},{"id":384194,"name":"Hugh E. Criswell","orcid":null,"position":3,"is_corresponding":false},{"id":612681,"name":"Kristin Hamre","orcid":"0000-0002-8302-3827","position":4,"is_corresponding":false},{"id":613102,"name":"Jessica L. Osterman","orcid":null,"position":5,"is_corresponding":false},{"id":592324,"name":"A. Leslie Morrow","orcid":"0000-0003-4441-956X","position":6,"is_corresponding":false},{"id":613103,"name":"Mary E. Wilkie","orcid":null,"position":7,"is_corresponding":false},{"id":370795,"name":"Gregg E. Homanics","orcid":"0000-0003-3641-8153","position":8,"is_corresponding":false},{"id":384195,"name":"George R. Breese","orcid":null,"position":9,"is_corresponding":false},{"id":593237,"name":"Todd K. O’Buckley","orcid":"0000-0001-8723-734X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:45.339291Z","pmid":null,"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":[]}