Authors
Beibei Peng, Xu Gao, Yan Chen, Yushi Xin, Yuxiao Zhang, Kexin Yu, Mingli Lu, Wenyan Li, Deqi Yang, Chaofei Bao, Shuai Liu
Published in
Science advances. Volume 12. Issue 39. Pages eaee1476. Sep 25, 2026. Epub Sep 23, 2026.
Abstract
Anorexia nervosa (AN) is a psychiatric disorder with a high mortality rate. The compulsive nature of the disorder leads to an emerging dopamine (DA)-centered 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 naïve 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.
PMID:
42777039
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.
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