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A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii

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Abstract

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTSLepRb) neurons notably activated breathing. Moreover, stimulation of NTSLepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTSLepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTSLepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTSLepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca2+ transients in most NTSLepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS–LPBN–preBötC circuit.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31800981 and 31971058), the Natural Science Foundation of Hebei Province for Distinguished Young Scholars (H2020206509), and a Hebei Province Government Grant (CXZZBS2020119).

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Authors and Affiliations

  1. Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China

    Hongxiao Yu, Luo Shi, Shirui Jun, Yinchao Hao, Shuang Wang, Xiang Zhang, Sheng Wang & Fang Yuan

  2. Core Facilities and Centers, Institute of Medicine and Health, Hebei Medical University, Shijiazhuang, 050017, Hebei, China

    Jinting Chen

  3. School of Nursing, Hebei Medical University, Shijiazhuang, 050000, Hebei, China

    Congrui Fu

  4. Department of Orthodontics, College of Stomatology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China

    Haiyan Lu

  5. Hebei Key Laboratory of Neurophysiology, Shijiazhuang, 050017, Hebei, China

    Sheng Wang & Fang Yuan

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  1. Hongxiao Yu
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Yu, H., Shi, L., Chen, J. et al. A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii. Neurosci. Bull. 38, 149–165 (2022). https://doi.org/10.1007/s12264-021-00742-4

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