Liuqi Shao1  · Yake Ji1  · Hongxiao Yu1  · Zixuan Cheng1  · Fanrao Kong1  · Xiaoyi Wang1  · Bingwen Zhang2  · Yinchang Wang1  · Yimeng Song1  · Fang Yuan1  · Congrui Fu2  · Sheng Wang1,3

1 Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China 

2 Nursing School, Hebei Medical University, Shijiazhuang 050031, China 

3 Hebei Key Laboratory of Brain Science and Brain‑Inspired Intelligence, Hebei Medical University, Shijiazhuang 050017, China

Abstract

Central respiratory chemoreception is a vital homeostatic mechanism maintaining arterial blood gas levels. Central respiratory chemoreceptors in the retrotrapezoid nucleus (RTN) and nucleus tractus solitarius (NTS) form interconnected circuits to regulate respiratory homeostasis. We hypothesized that NTS GABAergic neurons (NTS^GABA) modulate hypercapnic ventilatory responses by targeting ventrolateral medulla Phox2b neurons (VLM^Phox2b), particularly Phox2b-expressing RTN neurons. Stimulation of NTS^GABA neurons significantly attenuated CO₂-evoked ventilatory responses, accompanied by a reduction in CO₂-activated Phox2b-expressing RTN neurons. Neural tracing revealed that monosynaptic inputs to the VLM^Phox2b neurons primarily originate from the ventrolateral and dorsolateral subdivisions of the NTS. Photostimulation of NTS^GABA neurons retrogradely labeled from the VLM markedly suppressed respiratory drive, while chemogenetic activation of these neurons induced hypoventilation, increased spontaneous apnea, and attenuated hypercapnic ventilatory response. These findings demonstrate that activation of the NTS-VLM inhibitory circuit diminishes respiratory motor output, offering novel insights into the regulatory mechanisms of respiratory homeostasis.

Keywords

Central respiratory chemoreceptor; GABA; Respiratory center; Nucleus tractus solitarius; Neural circuit

[SpringerLink]