{"doi":"10.1101/2020.12.15.422912","title":"CRISPR knockdown of GABA <sub>A</sub> alpha3 subunits on thalamic reticular neurons enhances deep sleep","abstract":"Abstract Identification of mechanisms which increase deep sleep could lead to novel treatments which promote the restorative effects of sleep. Here, knockdown of the α3 GABA A -receptor subunit from parvalbumin neurons in the thalamic reticular nucleus using CRISPR-Cas9 gene editing increased the thalamocortical delta oscillations implicated in many health-promoting effects of sleep. Inhibitory synaptic currents were strongly reduced in vitro . Effects were most pronounced in the mouse sleep (light) period. Further analysis identified a novel deep-sleep state in mice prior to NREM-REM transitions which was preferentially affected by deletion of α3 subunits. Our results identify a functional role for GABA A receptors on Thalamic Reticular Nucleus neurons and suggest antagonism of α3 subunits as a strategy to enhance deep sleep. One Sentence Summary Selective genetic knockdown of the major α subunit of GABA A receptors present in the thalamic reticular nucleus enhanced deep sleep in mice.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131901,"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":0.9508,"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":586761,"name":"Chun Yang","orcid":"0000-0002-1979-0335","position":1,"is_corresponding":false},{"id":586762,"name":"Elena R. Tilli","orcid":"0000-0002-9590-0444","position":2,"is_corresponding":false},{"id":348208,"name":"Fumi Katsuki","orcid":"0000-0002-1411-6317","position":3,"is_corresponding":false},{"id":348202,"name":"James T Mckenna","orcid":"0000-0002-9710-3553","position":4,"is_corresponding":false},{"id":348205,"name":"James M. McNally","orcid":"0000-0002-6043-8560","position":5,"is_corresponding":false},{"id":348210,"name":"Ritchie E. Brown","orcid":"0000-0002-7164-4132","position":6,"is_corresponding":false},{"id":348212,"name":"Radhika Basheer","orcid":"0000-0002-4052-6897","position":7,"is_corresponding":false},{"id":348204,"name":"David S. Uygun","orcid":"0000-0002-6592-3223","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:16:07.542484Z","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":[]}