{"doi":"10.1101/2025.09.12.675848","title":"BDNF receptor balance gates AgRP-to-PVH fiber density and stimulation-evoked feeding across caloric states","abstract":"Abstract Agouti-related peptide (AgRP) neurons show opposite pairings of anatomy and output across caloric states. In mice, 24-h caloric restriction (CR) increases AgRP-to-paraventricular hypothalamus (PVH) fiber density without increasing stimulation-evoked feeding, whereas 5-day high-fat diet (HFD) reduces fiber density yet increases stimulation-evoked feeding, including during PVH terminal stimulation. PVH Bdnf rises acutely under both challenges and remains elevated with sustained HFD. Receptor expression shifts with state: in AgRP neurons, CR increases TrkB transcripts, whereas HFD increases p75NTR transcripts. AgRP-specific deletions define directional roles: TrkB loss reduces AgRP-to-PVH fiber density and yields larger stimulation-evoked feeding, whereas p75NTR loss increases fiber density and limits responses. Thus, a TrkB/p75NTR balance in AgRP neurons provides rheostat-like control over the relationship between circuit structure and stimulation-evoked feeding across caloric states, identifying TrkB and p75NTR as tractable molecular handles for probing state-dependent control of AgRP circuit output. Highlights CR increases AgRP→PVH fibers without boosting evoked feeding HFD retracts AgRP→PVH fibers and amplifies evoked feeding PVH Bdnf rises acutely in response to CR or HFD; elevation persists only with HFD AgRP TrkB ↑ with CR, p75NTR ↑ with HFD; AgRP specific knockouts of these receptors define floor and ceiling PVH axon innervation/evoked feeding","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":575070,"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":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1483397,"name":"Sara K Michel-Le","orcid":null,"position":1,"is_corresponding":false},{"id":877305,"name":"Elizabeth Godschall","orcid":"0000-0002-9719-5048","position":2,"is_corresponding":false},{"id":1483398,"name":"Shishir S Sriramoju","orcid":null,"position":3,"is_corresponding":false},{"id":1483399,"name":"Margaret Nunnaly","orcid":null,"position":4,"is_corresponding":false},{"id":1483400,"name":"Sophia Ogilvie","orcid":null,"position":5,"is_corresponding":false},{"id":1421761,"name":"K. West","orcid":null,"position":6,"is_corresponding":false},{"id":1483401,"name":"O. Li","orcid":null,"position":7,"is_corresponding":false},{"id":1483402,"name":"L. Vo","orcid":null,"position":8,"is_corresponding":false},{"id":1483077,"name":"Taha Buğra Güngül","orcid":"0000-0001-7632-4456","position":9,"is_corresponding":false},{"id":1483403,"name":"Prathik Reddy Nalamalapu","orcid":null,"position":10,"is_corresponding":false},{"id":1483404,"name":"Marcos Torales Montes","orcid":null,"position":11,"is_corresponding":false},{"id":1483405,"name":"Lloyd Choi","orcid":null,"position":12,"is_corresponding":false},{"id":258936,"name":"John N. Campbell","orcid":"0000-0002-3943-8312","position":13,"is_corresponding":false},{"id":411671,"name":"Ali D. Güler","orcid":"0000-0001-8218-850X","position":14,"is_corresponding":false},{"id":411670,"name":"Christopher D. Deppmann","orcid":"0000-0002-6591-1767","position":15,"is_corresponding":false},{"id":896135,"name":"O. Yipkin Calhan","orcid":"0000-0001-5630-6533","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"41000738","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":[]}