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Adv."],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:p>Anorexia nervosa (AN) is a psychiatric disorder with a high mortality rate. The compulsive nature of the disorder leads to an emerging dopamine (DA)\u2013centered hypothesis. However, the circuit mechanism of AN remains elusive. By examining a pontomesencephalic-mesolimbic circuit, which is implicated in anorexia-like and reinforcement behaviors in na\u00efve mice, we found that this pathway modulates activity-based anorexia (ABA), a well-established animal model of AN. Specifically, glutamatergic lateral parabrachial nucleus (LPBN) neurons indirectly inhibited medial ventral tegmental area (VTA) DA neurons through local GABAergic interneurons. Chronic activation of the LPBN-VTA circuit exacerbated ABA symptoms, whereas circuit suppression alleviated them, demonstrating its sufficiency and necessity. Moreover, VTA DA neurons exhibited impaired high-conductance calcium- and voltage-dependent potassium (BK) channel currents. Pharmacological enhancement of this channel improved the retention rate in ABA mice. Our results elucidate the critical role of the LPBN-VTA circuit and potential channel pathology, which may serve as a key to the development of drug treatments and intervention strategies for AN.<\/jats:p>","DOI":"10.1126\/sciadv.aee1476","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:59:49Z","timestamp":1790186389000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A pontomesencephalic-mesolimbic circuit modulates activity-based anorexia"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3836-0768","authenticated-orcid":true,"given":"Beibei","family":"Peng","sequence":"first","affiliation":[{"name":"Shanghai Changning Mental Health Center, Affiliated Mental Health Center, East China Normal University, Shanghai 200335, China."},{"name":"NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai, Shanghai 200062, 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