{"doi":"10.1111/acer.15412","title":"Optogenetic inhibition of light‐captured alcohol‐taking striatal engrams facilitates extinction and suppresses reinstatement","abstract":"BACKGROUND: Alcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol-seeking and -taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol-seeking and -taking behaviors and determine how they may affect one another. METHODS: Using FLiCRE (Fast Light and Calcium-Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant self-administration (OSA), we tagged striatal neurons activated during alcohol-taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol-taking neurons, permitting loss-of-function manipulations. RESULTS: We found that the inhibition of OSA-tagged alcohol-taking neurons decreased both alcohol-seeking and -taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA-tagged alcohol-taking neurons during extinction training facilitated the extinction of alcohol-seeking behaviors. Furthermore, inhibition of these OSA-tagged alcohol-taking neurons suppressed the reinstatement of alcohol-seeking behaviors, but, interestingly, it did not significantly suppress alcohol-taking behaviors during reinstatement. CONCLUSIONS: Our findings suggest that alcohol-taking neurons are crucial for future alcohol-seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.","journal":"Alcohol Clinical and Experimental Research","year":2024,"id":428927,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":672774,"name":"Xueyi Xie","orcid":"0000-0002-2349-1223","position":1,"is_corresponding":false},{"id":657122,"name":"Zhenbo Huang","orcid":"0000-0003-4857-5500","position":2,"is_corresponding":false},{"id":299575,"name":"Lian He","orcid":"0000-0002-8842-235X","position":3,"is_corresponding":false},{"id":437986,"name":"Eric A. Bancroft","orcid":"0000-0002-5857-7625","position":4,"is_corresponding":false},{"id":672778,"name":"Xuehua Wang","orcid":"0000-0002-5317-6822","position":5,"is_corresponding":false},{"id":407257,"name":"Tran B. Nguyen","orcid":"0000-0001-9206-4359","position":6,"is_corresponding":false},{"id":437987,"name":"Rahul Srinivasan","orcid":"0000-0003-0237-6602","position":7,"is_corresponding":false},{"id":139030,"name":"Yubin Zhou","orcid":"0000-0001-7962-0517","position":8,"is_corresponding":false},{"id":657125,"name":"Jun Wang","orcid":"0000-0002-0085-4722","position":9,"is_corresponding":false},{"id":984442,"name":"Valerie Vierkant","orcid":"0000-0001-7457-497X","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:59:02.165535Z","pmid":"39095328","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":[]}