The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.T...The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.展开更多
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 prese...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-ex-pressing NTS(NTS^(LepRb))neurons notably activated breathing.Moreover,stimulation of NTS^(LepRb) 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 NTS^(LepRb) neurons,but also activated LPBN neurons projecting to the preBotzinger complex(preBotC).By contrast,ablation of NTS^pRb 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-preBdtC circuit.展开更多
基金supported by the National Natural Science Foundation of China(31971058 and 31571174)the Youth Fund for Scientific and Technological Research in Higher Education Institutions of Hebei Province(QN2019019)the Youth Science and Technology Talent Support Program of Natural Science in Hebei Medical University(CYQD201907)。
文摘The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.
基金supported by the National Natural Science Foundation of China(31800981 and 31971058)the Natural Science Foundation of Hebei Province for Distinguished Young Scholars(H2020206509)a Hebei Province Government Grant(CXZZBS2020119).
文摘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-ex-pressing NTS(NTS^(LepRb))neurons notably activated breathing.Moreover,stimulation of NTS^(LepRb) 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 NTS^(LepRb) neurons,but also activated LPBN neurons projecting to the preBotzinger complex(preBotC).By contrast,ablation of NTS^pRb 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-preBdtC circuit.