PDF(Pubmed)
Abstract：
Transcutaneous auricular vagus nerve stimulation (taVNS) targets subcutaneous axons in the auricular branch of the vagus nerve at the outer ear. Its non-invasive nature makes it a potential treatment for various disorders. taVNS induces neuromodulatory effects within the nucleus of the solitary tract (NTS), and due to its widespread connectivity, the NTS acts as a gateway to elicit neuromodulation in both higher-order brain regions and other brainstem nuclei (e.g. spinal trigeminal nucleus; Sp5). Our objective was to examine stimulation parameters on single-neuron electrophysiological responses in α-chloralose-anaesthetized Sprague-Dawley rats within NTS and Sp5. taVNS was also compared to traditional cervical VNS (cVNS) on single neuronal activation. Specifically, electrophysiological extracellular recordings were evaluated for a range of frequency and intensity parameters (20-250 Hz, 0.5-1.0 mA). Neurons were classified as positive, negative or non-responders based on increased activity, decreased activity or no response during stimulation, respectively. Frequency-dependent analysis showed that 20 and 100 Hz generated the highest proportion of positive responders in NTS and Sp5 with 1.0 mA intensities eliciting the greatest magnitude of response. Comparisons between taVNS and cVNS revealed similar parameter-specific activation for caudal NTS neuronal populations; however, individual neurons showed different activation profiles. The latter suggests that cVNS and taVNS send afferent input to NTS via different neuronal pathways. This study demonstrates differential parameter-specific taVNS responses and begins an investigation of the mechanisms responsible for taVNS modulation. Understanding the neuronal pathways responsible for eliciting neuromodulatory effects will enable more tailored taVNS treatments in various clinical disorders. KEY POINTS: Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non-invasive alternative to invasive cervical vagus nerve stimulation (cVNS) by activating vagal afferents in the ear to induce neuromodulation. Our study evaluated taVNS effects on neuronal firing patterns in the nucleus of the solitary tract (NTS) and spinal trigeminal nucleus (Sp5) and found that 20 and 100 Hz notably increased neuronal activity during stimulation in both nuclei. Increasing taVNS intensity not only increased the number of neurons responding in Sp5 but also increased the magnitude of response, suggesting a heightened sensitivity to taVNS compared to NTS. Comparisons between cVNS and taVNS revealed similar overall activation but different responses on individual neurons, indicating distinct neural pathways. These results show parameter-specific and nuclei-specific responses to taVNS and confirm that taVNS can elicit responses comparable to cVNS at the neuronal level, but it does so through different neuronal pathways.
摘要：
经皮耳迷走神经刺激（taVNS）靶向外耳迷走神经耳支的皮下轴突。它的非侵入性使其成为各种疾病的潜在治疗方法。taVNS在孤束核（NTS）内诱导神经调节作用，由于其广泛的连通性，NTS充当在高级脑区和其他脑干核(例如脊髓三叉神经核;Sp5)引起神经调节的门户。我们的目的是检查NTS和Sp5中α-氯醛糖麻醉的Sprague-Dawley大鼠单神经元电生理反应的刺激参数。还将taVNS与传统宫颈VNS(cVNS)在单个神经元激活上进行比较。具体来说,对一系列频率和强度参数(20-250Hz，0.5-1.0mA)。神经元被归类为阳性，基于活动增加的负面或无反应者，刺激期间活动减少或无反应，分别。频率依赖性分析表明，在NTS和Sp5中，20和100Hz产生的阳性反应者比例最高，1.0mA强度引起最大程度的反应。taVNS和cVNS之间的比较揭示了尾端NTS神经元群体相似的参数特异性激活；然而，单个神经元显示不同的激活谱。后者表明cVNS和taVNS通过不同的神经元途径向NTS发送传入输入。这项研究证明了不同的参数特异性taVNS反应，并开始研究负责taVNS调节的机制。了解负责引发神经调节作用的神经元途径将能够在各种临床疾病中进行更量身定制的taVNS治疗。要点：经皮耳迷走神经刺激（taVNS）通过激活耳朵中的迷走神经传入以诱导神经调节，提供了一种非侵入性替代侵入性颈迷走神经刺激（cVNS）。我们的研究评估了taVNS对孤束核（NTS）和三叉神经脊髓核（Sp5）中神经元放电模式的影响，发现20和100Hz在两个核刺激期间显着增加了神经元活性。taVNS强度的增加不仅增加了Sp5中响应的神经元数量，而且增加了响应的幅度，表明与NTS相比，对taVNS的敏感性提高。cVNS和taVNS之间的比较揭示了相似的整体激活，但对单个神经元的反应不同。显示不同的神经通路。这些结果显示了对taVNS的参数特异性和细胞核特异性反应，并证实taVNS可以在神经元水平上引发与cVNS相当的反应，但它是通过不同的神经元途径实现的。
