Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract
Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract
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DOI：
10.1152/ajpheart.00070.2017
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发表时间：
2017-08-01
影响因子：
4.8
通讯作者：
Cantrell, Nathan
中科院分区：
文献类型：
--
作者：
Beaumont, Eric;Campbell, Regenia P.;Cantrell, Nathan
迷走神经刺激（VNS）目前用于治疗耐药性癫痫、抑郁症和心力衰竭患者。在慢性VNS中使用的轻度强度表明涉及初级内脏传入和中枢神经系统激活。在这里，我们测量了神经元的活动在孤束核（NTS）在麻醉大鼠使用临床风格的VNS。我们的主要发现表明，在阈值心动过缓强度的VNS激活NTS神经元放电的三分之一的NTS神经元。这种VNS直接激活只有髓鞘迷走神经传入投射到二级NTS神经元。然而，大多数VNS诱导的NTS活动与迷走神经刺激不同步。因此，VNS激活NTS神经元的非同步活动，这些神经元是迷走神经传入C纤维的二级神经元，以及仅由迷走神经多突触激活的高阶NTS神经元。总体而言，心血管敏感和不敏感的NTS神经元被VNS激活：3/4的神经元与单突触迷走神经A纤维传入，6/42的神经元与单突触迷走神经C纤维传入，和16/21多突触NTS神经元。刺激，迷走神经A纤维间接激活C纤维神经元在VNS。升高的自发尖峰在数量上远高于同步活动，并扩展到非刺激期。令人惊讶的是，许多多突触NTS神经元对临床研究中使用的心动过缓强度的一半作出反应，表明有髓鞘迷走神经传入的子集足以引起VNS间接激活。我们的研究发现了一种有髓鞘的迷走神经传入驱动，间接激活NTS神经元，从而激活NTS以外的中枢通路，并支持重新考虑迷走神经传入对大脑的贡献，支持治疗效果。新&值得注意的是急性迷走神经刺激提高了位于孤束内侧核的神经元的活性。这种刺激直接激活只有髓鞘迷走神经传入，但间接激活了亚群的二级和更高级的神经元，这表明传入机制和中枢神经元激活可能是负责迷走神经刺激的疗效。
Vagus nerve stimulation (VNS) currently treats patients with drug-resistant epilepsy, depression, and heart failure. The mild intensities used in chronic VNS suggest that primary visceral afferents and central nervous system activation are involved. Here, we measured the activity of neurons in the nucleus of the solitary tract (NTS) in anesthetized rats using clinically styled VNS. Our chief findings indicate that VNS at threshold bradycardic intensity activated NTS neuron discharge in one-third of NTS neurons. This VNS directly activated only myelinated vagal afferents projecting to second-order NTS neurons. Most VNS-induced activity in NTS, however, was unsynchronized to vagal stimuli. Thus, VNS activated unsynchronized activity in NTS neurons that were second order to vagal afferent C-fibers as well as higher-order NTS neurons only polysynaptically activated by the vagus. Overall, cardiovascular-sensitive and -insensitive NTS neurons were similarly activated by VNS: 3/4 neurons with monosynaptic vagal A-fiber afferents, 6/42 neurons with monosynaptic vagal C-fiber afferents, and 16/21 polysynaptic NTS neurons. Provocatively, vagal A-fibers indirectly activated C-fiber neurons during VNS. Elevated spontaneous spiking was quantitatively much higher than synchronized activity and extended well into the periods of nonstimulation. Surprisingly, many polysynaptic NTS neurons responded to half the bradycardic intensity used in clinical studies, indicating that a subset of myelinated vagal afferents is sufficient to evoke VNS indirect activation. Our study uncovered a myelinated vagal afferent drive that indirectly activates NTS neurons and thus central pathways beyond NTS and support reconsideration of brain contributions of vagal afferents underpinning of therapeutic impacts.NEW & NOTEWORTHY Acute vagus nerve stimulation elevated activity in neurons located in the medial nucleus of the solitary tract. Such stimuli directly activated only myelinated vagal afferents but indirectly activated a subpopulation of second-and higher-order neurons, suggesting that afferent mechanisms and central neuron activation may be responsible for vagus nerve stimulation efficacy.