{"doi":"10.1038/s41586-024-07138-0","title":"Crym-positive striatal astrocytes gate perseverative behaviour","abstract":"Abstract Astrocytes are heterogeneous glial cells of the central nervous system 1–3 . However, the physiological relevance of astrocyte diversity for neural circuits and behaviour remains unclear. Here we show that a specific population of astrocytes in the central striatum expresses μ-crystallin (encoded by Crym in mice and CRYM in humans) that is associated with several human diseases, including neuropsychiatric disorders 4–7 . In adult mice, reducing the levels of μ-crystallin in striatal astrocytes through CRISPR–Cas9-mediated knockout of Crym resulted in perseverative behaviours, increased fast synaptic excitation in medium spiny neurons and dysfunctional excitatory–inhibitory synaptic balance. Increased perseveration stemmed from the loss of astrocyte-gated control of neurotransmitter release from presynaptic terminals of orbitofrontal cortex–striatum projections. We found that perseveration could be remedied using presynaptic inhibitory chemogenetics 8 , and that this treatment also corrected the synaptic deficits. Together, our findings reveal converging molecular, synaptic, circuit and behavioural mechanisms by which a molecularly defined and allocated population of striatal astrocytes gates perseveration phenotypes that accompany neuropsychiatric disorders 9–12 . Our data show that Crym -positive striatal astrocytes have key biological functions within the central nervous system, and uncover astrocyte–neuron interaction mechanisms that could be targeted in treatments for perseveration.","journal":"Nature","year":2024,"id":418603,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"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":267266,"name":"Joselyn S. Soto","orcid":"0000-0002-5869-9091","position":1,"is_corresponding":false},{"id":1207058,"name":"Kay E. Linker","orcid":"0000-0002-8825-6187","position":2,"is_corresponding":false},{"id":669087,"name":"Stefanie L. Moye","orcid":"0000-0002-9699-5406","position":3,"is_corresponding":false},{"id":344710,"name":"Yasaman Jami‐Alahmadi","orcid":"0000-0001-8289-2222","position":4,"is_corresponding":false},{"id":325891,"name":"Anthony E. Jones","orcid":"0000-0003-2058-6021","position":5,"is_corresponding":false},{"id":242293,"name":"Ajit S. Divakaruni","orcid":"0000-0002-2528-9651","position":6,"is_corresponding":false},{"id":226817,"name":"Riki Kawaguchi","orcid":"0000-0002-2489-4825","position":7,"is_corresponding":false},{"id":14958,"name":"James A. Wohlschlegel","orcid":"0000-0003-3399-901X","position":8,"is_corresponding":false},{"id":233476,"name":"Baljit S. Khakh","orcid":"0000-0002-0939-1218","position":9,"is_corresponding":false},{"id":637431,"name":"Matthias Ollivier","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:57:09.067930Z","pmid":"38418885","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":[]}