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

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 preBotzinger complex (preBotC). 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-preBotC circuit.

Automated summary

The study demonstrates that neurons expressing LepRb in the nucleus tractus solitarii (NTS) play a key role in respiratory control, with leptin potentiating breathing via an NTS-LPBN-preBotC circuit. Stimulation of NTSLepRb neurons notably activates breathing, while ablation of NTSLepRb neurons projecting to the LPBN eliminates the enhanced effect.