@article {69074,
	title = {Vagal sensory neurons mediate the Bezold-Jarisch reflex and induce syncope.},
	journal = {Nature},
	volume = {623},
	year = {2023},
	month = {2023 Nov 01},
	pages = {387-396},
	abstract = {<p>Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders. The Bezold-Jarisch reflex (BJR), first described 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 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 syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels.</p>
},
	keywords = {Area Postrema, Bradycardia, Cardiac Output, Low, Echocardiography, Heart, Heart Rate, Humans, Hypotension, Laser-Doppler Flowmetry, Nerve Net, Reflex, Sensory Receptor Cells, Single-Cell Gene Expression Analysis, Syncope, vagus nerve},
	issn = {1476-4687},
	doi = {10.1038/s41586-023-06680-7},
	author = {Lovelace, Jonathan W and Ma, Jingrui and Yadav, Saurabh and Chhabria, Karishma and Shen, Hanbing and Pang, Zhengyuan and Qi, Tianbo and Sehgal, Ruchi and Zhang, Yunxiao and Bali, Tushar and Vaissiere, Thomas and Tan, Shawn and Liu, Yuejia and Rumbaugh, Gavin and Ye, Li and Kleinfeld, David and Stringer, Carsen and Augustine, Vineet}
}
