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Despite its high morbidity and mortality, the neural mechanisms underlying AN remain poorly defined, largely because no animal model has fully recapitulated its core behavioral manifestations. Here, we demonstrate that aberrant activation of glutamatergic neurons in the mediobasal hypothalamus (MBH) is sufficient to induce AN-like phenotypes in mice, including self-starvation leading to death, hyperactivity, anhedonia, social avoidance, and heightened anxiety, which were reproduced by targeted activation of MBH neurons expressing steroidogenic factor 1 (SF1)\/ estrogen receptor \u03b1 (ER\u03b1). Mechanistically, the AN-like phenotypes were rescued by ablating release of glutamate or brain-derived neurotrophic factor (BDNF). Conversely, BDNF overexpression in SF1\/ER\u03b1 neurons was sufficient to promote AN-like behaviors through increasing glutamate release. Thus, BDNF-dependent enhancement of glutamatergic signaling from SF1\/ER\u03b1 neurons drives AN-associated phenotypes, providing a potential target for therapeutic intervention.<\/jats:p>","DOI":"10.64898\/2026.02.07.704578","type":"posted-content","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:10:32Z","timestamp":1770747032000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of a neural basis orchestrating anorexia nervosa-like phenotypes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3728-3377","authenticated-orcid":false,"given":"Cunjin","family":"Su","sequence":"first","affiliation":[{"name":"Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, TX, 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