{"doi":"10.1016/j.cub.2023.06.070","title":"Anterior hypothalamic parvalbumin neurons are glutamatergic and promote escape behavior","abstract":"The anterior hypothalamic area (AHA) is a critical structure for defensive responding. Here, we identified a cluster of parvalbumin-expressing neurons in the AHA (AHA PV ) that are glutamatergic with fast-spiking properties and send axonal projections to the dorsal premammillary nucleus (PMD). Using in vivo functional imaging, optogenetics, and behavioral assays, we determined the role of these AHA PV neurons in regulating behaviors essential for survival. We observed that AHA PV neuronal activity significantly increases when mice are exposed to a predator, and in a real-time place preference assay, we found that AHA PV neuron photoactivation is aversive. Moreover, activation of both AHA PV neurons and the AHA PV → PMD pathway triggers escape responding during a predator-looming test. Furthermore, escape responding is impaired after AHA PV neuron ablation, and anxiety-like behavior as measured by the open field and elevated plus maze assays does not seem to be affected by AHA PV neuron ablation. Finally, whole-brain metabolic mapping using positron emission tomography combined with AHA PV neuron photoactivation revealed discrete activation of downstream areas involved in arousal, affective, and defensive behaviors including the amygdala and the substantia nigra. Our results indicate that AHA PV neurons are a functional glutamatergic circuit element mediating defensive behaviors, thus expanding the identity of genetically defined neurons orchestrating fight-or-flight responses. Together, our work will serve as a foundation for understanding neuropsychiatric disorders triggered by escape such as post-traumatic stress disorder (PTSD).","journal":"Current Biology","year":2023,"id":329243,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1051873,"name":"Megan S. Anderson","orcid":"0000-0003-3629-5288","position":1,"is_corresponding":false},{"id":449147,"name":"Jordi Bonaventura","orcid":"0000-0002-4745-0151","position":2,"is_corresponding":false},{"id":942410,"name":"Aishwarya Jayan","orcid":"0009-0006-9760-7117","position":3,"is_corresponding":false},{"id":411249,"name":"Sarah Sarsfield","orcid":"0000-0002-0527-8154","position":4,"is_corresponding":false},{"id":1052435,"name":"Anjali Gajendiran","orcid":null,"position":5,"is_corresponding":false},{"id":323449,"name":"Michel Michaelides","orcid":"0000-0002-1552-7046","position":6,"is_corresponding":false},{"id":411250,"name":"Yeka Aponte","orcid":"0000-0002-5967-2579","position":7,"is_corresponding":false},{"id":412539,"name":"Brenton T. Laing","orcid":null,"position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T01:09:01.509601Z","pmid":"37490921","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":[]}