Vagal stimulation is emerging as the next frontier in bioelectronic medicine to modulate peripheral organ health and treat disease. The neuronal molecular phenotypes in the dorsal motor nucleus of the vagus (DMV) remain largely unexplored, limiting the potential for harnessing the DMV plasticity for therapeutic interventions. We developed a mesoscale single cell transcriptomics data from hundreds of DMV neurons under homeostasis and following physiological perturbations. Our results revealed that homeostatic DMV neuronal states can be organized into distinguishable input-output signal processing units. Remote ischemic preconditioning induced a distinctive shift in the neuronal states towards diminishing the role of inhibitory inputs, with concomitant changes in regulatory microRNAs miR-218a and miR-495. Chronic cardiac ischemic injury resulted in a dramatic shift in DMV neuronal states suggestive of enhanced neurosecretory function. We propose a DMV molecular network mechanism that integrates combinatorial neurotransmitter inputs from multiple brain regions and humoral signals to modulate cardiac health.

中文翻译：

---

迷走神经元对心脏缺血性损伤的输入输出信号处理可塑性

迷走神经刺激正在成为调节周围器官健康和治疗疾病的生物电子医学的下一个前沿领域。迷走神经背运动核（DMV）中的神经元分子表型仍未开发，限制了利用DMV可塑性进行治疗性干预的潜力。我们在稳态和生理扰动下，从数百个DMV神经元开发了中等规模的单细胞转录组学数据。我们的结果表明，稳态DMV神经元状态可以组织为可区分的输入输出信号处理单元。远程缺血预处理导致神经元状态发生显着变化，以减少抑制性输入的作用，同时伴随着调控性microRNA miR-218a和miR-495的变化。慢性心脏缺血性损伤导致DMV神经元状态发生剧烈变化，提示神经分泌功能增强。我们提出了一种DMV分子网络机制，该机制整合了来自多个大脑区域的组合神经递质输入和体液信号，以调节心脏健康。