A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii
A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii
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DOI：
10.1007/s12264-021-00742-4
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发表时间：
2021-07
影响因子：
5.6
通讯作者：
Hongxiao Yu;L. Shi;Jinting Chen;Shirui Jun;Yinchao Hao;Shuang Wang;Congrui Fu;Xiang Zhang
中科院分区：
文献类型：
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作者：
Hongxiao Yu;L. Shi;Jinting Chen;Shirui Jun;Yinchao Hao;Shuang Wang;Congrui Fu;Xiang Zhang
瘦素是一种脂肪细胞衍生的多肽激素，已被证明可以促进呼吸。然而，瘦素呼吸作用的中枢部位和回路机制仍不完全清楚。本研究旨在探讨孤束核(NTS)内表达瘦素受体b(LepRb)的神经元是否参与呼吸控制。对表达LepRb的NTS(NTSLepRb)神经元的化学发生和光发生刺激都显著地激活了呼吸。此外，刺激向臂旁外侧核(LPBN)投射的NTSLepRb神经元不仅能显著增加基础通气量，达到刺激所有NTSLepRb神经元的水平，而且还能激活投射到Prebötzinger复合体(PreböttC)的LPBN神经元。相反，消融投射至LPBN的NTSLepRb神经元可显著消除刺激NTSLepRb神经元引起的呼吸增强效应。在脑干脑片上，大多数NTSLepRb神经元的膜电位迅速去极化，自发放电频率增加，钙瞬变加快。因此，瘦素最有可能通过NTS-LPBN-PrebötC环路增强NTS的呼吸。
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 NTSLepRbneurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTSLepRbneurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTSLepRbneurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTSLepRbneuron 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 NTSLepRbneurons. Therefore, leptin potentiates breathing in the NTS most likelyviaan NTS–LPBN–preBötC circuit.