kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents.
kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents.
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DOI：
10.1016/j.brs.2022.09.015
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发表时间：
2022-11
影响因子：
7.7
通讯作者：
Zanos, Stavros
中科院分区：
文献类型：
--
作者：
Chang, Yao-Chuan;Ahmed, Umair;Jayaprakash, Naveen;Mughrabi, Ibrahim;Lin, Qihang;Wu, Yi-Chen;Gerber, Michael;Abbas, Adam;Daytz, Anna;Gabalski, Arielle H.;Ashville, Jason;Dokos, Socrates;Rieth, Loren;Datta-Chaudhuri, Timir;Tracey, Kevin J.;Guo, Tianruo;Al -Abed, Yousef;Zanos, Stavros
迷走神经反射通过传入和传出神经元和神经纤维调节内脏器官和系统的稳态。小型、无髓鞘的 C 型传入神经占迷走神经纤维的 80% 以上，形成肠道、肺、心脏和血管以及免疫系统的自主反射感觉弧。 C传入神经的选择性生物电子激活可用于机械研究和治疗涉及迷走神经反射的外周器官疾病，但尚未实现。我们使用 kHz 频率刺激序列刺激大鼠和小鼠的迷走神经。使用神经元 c-Fos 表达、生理和神经纤维反应、光遗传学和计算方法评估刺激效果。 30 分钟的间歇性 kHz 刺激会激活脑干中的特定运动神经元，并优先激活感觉迷走神经元。在足够高的频率（> 5 kHz）和特定范围内的强度（大鼠中为激活阈值 T 的 7-10 倍；小鼠中为 15-25 × T）时，C 传入神经被激活，而较大的 A 纤维和 B 纤维被阻断。这是通过测量纤维对 kHz 刺激序列的特异性急性生理反应，并通过探测脉冲诱发的复合动作电位评估 kHz 刺激序列周围的纤维兴奋性来确定的。 C 传入神经选择性激活的各个方面可以在神经纤维的计算模型中通过纤维尺寸和髓磷脂如何塑造钠通道对 kHz 频率刺激的响应来解释。 kHz 刺激是一种神经调节策略，可通过较大的迷走神经纤维稳健且选择性地激活与生理稳态和疾病有关的迷走神经 C 传入神经。
Vagal reflexes regulate homeostasis in visceral organs and systems through afferent and efferent neurons and nerve fibers. Small, unmyelinated, C-type afferents comprise over 80% of fibers in the vagus and form the sensory arc of autonomic reflexes of the gut, lungs, heart and vessels and the immune system. Selective bioelectronic activation of C-afferents could be used to mechanistically study and treat diseases of peripheral organs in which vagal reflexes are involved, but it has not been achieved. We stimulated the vagus in rats and mice using trains of kHz-frequency stimuli. Stimulation effects were assessed using neuronal c-Fos expression, physiological and nerve fiber responses, optogenetic and computational methods. Intermittent kHz stimulation for 30 min activates specific motor and, preferentially, sensory vagus neurons in the brainstem. At sufficiently high frequencies (>5 kHz) and at intensities within a specific range (7–10 times activation threshold, T, in rats; 15–25 × T in mice), C-afferents are activated, whereas larger, A- and B-fibers, are blocked. This was determined by measuring fiber-specific acute physiological responses to kHz stimulus trains, and by assessing fiber excitability around kHz stimulus trains through compound action potentials evoked by probing pulses. Aspects of selective activation of C-afferents are explained in computational models of nerve fibers by how fiber size and myelin shape the response of sodium channels to kHz-frequency stimuli. kHz stimulation is a neuromodulation strategy to robustly and selectively activate vagal C-afferents implicated in physiological homeostasis and disease, over larger vagal fibers.
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