Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
Department of Pharmacology and Physiology, Institute of Biomedical Engineering, University of Montreal, Montreal, Quebec, Canada.
J Physiol. 2024 Aug;602(16):4027-4052. doi: 10.1113/JP286680. Epub 2024 Jul 19.
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.
经皮耳迷走神经刺激(taVNS)作用于耳廓迷走神经的耳分支中的皮下轴突。由于其非侵入性,它成为治疗各种疾病的潜在手段。taVNS 在孤束核(NTS)中诱导神经调节作用,由于其广泛的连通性,NTS 作为引发高级脑区和其他脑干核(如脊髓三叉神经核;Sp5)神经调节的门户。我们的目标是在α-氯醛麻醉的 Sprague-Dawley 大鼠的 NTS 和 Sp5 中检查刺激参数对单个神经元电生理反应的影响。还将 taVNS 与传统的颈部迷走神经刺激(cVNS)进行了比较,以观察其对单个神经元的激活作用。具体来说,评估了一系列频率和强度参数(20-250 Hz,0.5-1.0 mA)的电生理细胞外记录。根据刺激期间活动增加、活动减少或无反应,将神经元分类为阳性、阴性或无反应者。频率依赖性分析表明,20 和 100 Hz 在 NTS 和 Sp5 中产生最高比例的阳性反应者,1.0 mA 强度产生最大的反应幅度。taVNS 和 cVNS 之间的比较显示出尾部 NTS 神经元群体的相似的参数特异性激活;然而,单个神经元显示出不同的激活模式。后者表明,cVNS 和 taVNS 通过不同的神经元通路向 NTS 发送传入输入。这项研究证明了 taVNS 具有不同的参数特异性反应,并开始研究负责 taVNS 调节的机制。了解引起神经调节作用的神经元通路将使 taVNS 在各种临床疾病中的治疗更加个性化。关键点:经皮耳迷走神经刺激(taVNS)通过刺激耳朵中的迷走神经传入纤维来激活迷走神经,为侵入性的颈部迷走神经刺激(cVNS)提供了一种非侵入性的替代方法,从而诱导神经调节。我们的研究评估了 taVNS 对孤束核(NTS)和脊髓三叉神经核(Sp5)中神经元放电模式的影响,发现 20 和 100 Hz 在两个核中均显著增加了刺激期间神经元的活动。增加 taVNS 强度不仅增加了 Sp5 中反应神经元的数量,还增加了反应幅度,表明与 NTS 相比,taVNS 的敏感性更高。cVNS 和 taVNS 之间的比较显示出总体相似的激活,但单个神经元的反应不同,表明存在不同的神经通路。这些结果显示 taVNS 对刺激有参数特异性和核特异性反应,并证实 taVNS 可以在神经元水平上产生与 cVNS 相当的反应,但它通过不同的神经元通路来实现。
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