Circuit Mechanisms Underlying the Contribution of Leptin Receptor-Expressing Neurons in the Nucleus Tractus Solitarius to Ventilatory Homeostasis
Yinchao Hao1,2 · Mengchu Zhu1,3 · Hongxiao Yu1 · Xiang Zhang1 · Yishuo Shi1 · Lu Sun1 · Yaxin Hao1 · Yifei Huang1 · Lingxiao Yu1 · Sheng Wang1,4,5 · Dongxing Zhao6 · Fang Yuan1,4,5
1 Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China
2 Experimental Center for Teaching, Hebei Medical University, Shijiazhuang 050017, China
3 Department of Laboratory Diagnostics, Hebei Medical University, Shijiazhuang 050017, China
4 Hebei Key Laboratory of Brain Science and Brain-Inspired Intelligence, Shijiazhuang 050017, China
5 The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China
6 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510162, China
Abstract
Sleep apnea syndrome (SAS) is a prevalent disorder characterized by recurrent respiratory pauses during sleep; however, the neural mechanisms governing respiratory stability remain poorly understood. In this study, we identify the ratio of sigh expiratory volume to eupneic expiratory volume as a potential predictor of post-sigh apnea in susceptible C57BL/6J mice. We demonstrate that leptin signaling within the nucleus tractus solitarius (NTS) is critical for maintaining respiratory drive and suppressing apnea. Chemogenetic activation of Leptin receptor b-expressing NTS (NTSLepRb) neurons significantly reduced apnea incidence, whereas their ablation exacerbated respiratory dysfunction. Moreover, NTSLepRb neurons mediate these effects through anatomically and functionally segregated projections to the dorsomedial hypothalamus and the lateral parabrachial nucleus. These findings define a specific leptin-mediated brainstem circuit that stabilizes respiratory output, providing new mechanistic insights and potential therapeutic targets for sleep-disordered breathing.
Keywords
Leptin; Nucleus tractus solitarius; Sleep apnea; Neural circuit
