小柯机器人

美国加州大学Vineet Augustine团队近期取得重要工作进展，他们研究发现迷走感觉神经元介导Bezold-Jarisch反射并诱发晕厥。相关研究成果2023年11月1日在线发表于《自然》杂志上。

据介绍，内脏感觉通路介导稳态反射，稳态反射的功能障碍会导致许多神经系统疾病。Bezold–Jarisch反射（BJR）于1867年被首次描述，这是一种心脏抑制性反射，据推测由迷走神经感觉神经元（VSN）介导，也会引发晕厥。然而，心脏VSN的分子特征、解剖组织、生理特征和行为影响扔不清楚。

研究人员利用单细胞RNA测序数据和HYBRiD组织清除表明，表达神经肽的VSN Y受体Y2（NPY2R）主要连接心室壁和后壁区。NPY2R-VSN的光遗传学激活引发典型的三重BJR反应（低血压、心动过缓和呼吸抑制），并导致动物晕倒。高分辨率超声心动图和激光多普勒血流测量与行为观察的光刺激显示了临床晕厥中反映的一系列表型，包括心输出量减少、脑灌注不足、瞳孔扩张和翻白眼。大规模Neuropixels大脑记录和基于机器学习的建模表明，这种操作会导致大规模分布神经元群体的活动受到抑制，而自发行为运动的变化并不能解释这一点。

此外，心室周围区的双向操作具有推挽效应，抑制会导致更长的晕厥期和激活诱导的觉醒。最后，去除NPY2R VSN专门废除了BJR。

总之，这些结果证明了一种基因定义的心脏反射，它在生理、行为和神经网络水平上概括了人类晕厥的特征。

附：英文原文

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

Author: Lovelace, Jonathan W., Ma, Jingrui, Yadav, Saurabh, Chhabria, Karishma, Shen, Hanbing, Pang, Zhengyuan, Qi, Tianbo, Sehgal, Ruchi, Zhang, Yunxiao, Bali, Tushar, Vaissiere, Thomas, Tan, Shawn, Liu, Yuejia, Rumbaugh, Gavin, Ye, Li, Kleinfeld, David, Stringer, Carsen, Augustine, Vineet

Issue&Volume: 2023-11-01

Abstract: Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders1. The Bezold–Jarisch reflex (BJR), first described2,3 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 clearing4 to show that VSNs that express neuropeptideY 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.

DOI: 10.1038/s41586-023-06680-7

Source: https://www.nature.com/articles/s41586-023-06680-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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