{"doi":"10.7554/elife.69178","title":"Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats","abstract":"Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.","journal":"eLife","year":2021,"id":163655,"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":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9451,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":646031,"name":"Peter J. Schuette","orcid":"0000-0002-6308-6441","position":1,"is_corresponding":false},{"id":647115,"name":"Mimi Q La-Vu","orcid":null,"position":2,"is_corresponding":false},{"id":440140,"name":"Anita Torossian","orcid":"0000-0002-4965-1790","position":3,"is_corresponding":false},{"id":646033,"name":"Brooke C Tobias","orcid":"0000-0003-2043-9523","position":4,"is_corresponding":false},{"id":301286,"name":"Marta Čeko","orcid":"0000-0001-8679-8145","position":5,"is_corresponding":false},{"id":321262,"name":"Philip A. Kragel","orcid":"0000-0001-9463-6381","position":6,"is_corresponding":false},{"id":267301,"name":"Fernando MCV Reis","orcid":"0000-0002-0121-2887","position":7,"is_corresponding":false},{"id":683613,"name":"Shiyu Ji","orcid":"0000-0003-3413-5766","position":8,"is_corresponding":false},{"id":683614,"name":"Megha Sehgal","orcid":"0000-0003-1337-4063","position":9,"is_corresponding":false},{"id":267305,"name":"Sandra Maesta‐Pereira","orcid":"0000-0001-6522-8311","position":10,"is_corresponding":false},{"id":647114,"name":"Meghmik Chakerian","orcid":null,"position":11,"is_corresponding":false},{"id":681420,"name":"Alcino J. Silva","orcid":"0000-0002-1587-4558","position":12,"is_corresponding":false},{"id":646034,"name":"Newton S. Canteras","orcid":"0000-0002-7205-5372","position":13,"is_corresponding":false},{"id":226967,"name":"Tor D. Wager","orcid":"0000-0002-1936-5574","position":14,"is_corresponding":false},{"id":270098,"name":"Jonathan C. Kao","orcid":"0000-0002-9298-0143","position":15,"is_corresponding":false},{"id":267311,"name":"Avishek Adhikari","orcid":"0000-0002-9187-9211","position":16,"is_corresponding":false},{"id":683612,"name":"Weisheng Wang","orcid":"0009-0005-5271-6371","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:45:22.477398Z","pmid":"34468312","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":[]}