Vagal sensory neurons mediate the Bezold–Jarisch reflex and induce syncope

作者：Jonathan W. Lovelace, Jingrui Ma, Saurabh Yadav, Karishma Chhabria, Hanbing Shen, Zhengyuan Pang, Tianbo Qi, Ruchi Sehgal, Yunxiao Zhang, Tushar Bali, Thomas Vaissière, Shawn Zheng Kai Tan, Yuejia Liu, Gavin Rumbaugh, Li Ye, David Kleinfeld, Carsen Stringer, Vineet Augustine · 发表于：Nature · 年份：2023 · DOI：10.1038/s41586-023-06680-7 · 被引用次数：107 · 研究领域：Heart Rate Variability and Autonomic Control、Neuroscience of respiration and sleep、Circadian rhythm and melatonin

Abstract Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders 1 . The Bezold–Jarisch reflex (BJR), first described 2,3 in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing 4 to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses—hypotension, bradycardia and suppressed respiration—and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push–pull effect, with inhibition leading to longer s...