Yamamoto Kenta, Lalley Peter, Mifflin Steve
Department of Integrative Physiology, Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; and.
Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Am J Physiol Regul Integr Comp Physiol. 2015 Feb 15;308(4):R266-75. doi: 10.1152/ajpregu.00381.2014. Epub 2014 Dec 17.
Acute intermittent hypoxia (AIH) induces sympathetic and phrenic long-term facilitation (LTF), defined as a sustained increase in nerve discharge. We investigated the effects of AIH and acute intermittent optogenetic (AIO) stimulation of neurons labeled with AAV-CaMKIIa, hChR2(H134R), and mCherry in the nucleus of the solitary tract (NTS) of anesthetized, vagotomized, and mechanically ventilated rats. We measured renal sympathetic nerve activity (RSNA), phrenic nerve activity (PNA), power spectral density, and coherence, and we made cross-correlation measurements to determine how AIO stimulation and AIH affected synchronization between PNA and RSNA. Sixty minutes after AIH produced by ventilation with 10% oxygen in balanced nitrogen, RSNA and PNA amplitude increased by 80% and by 130%, respectively (P < 0.01). Sixty minutes after AIO stimulation, RSNA and PNA amplitude increased by 60% and 100%, respectively, (P < 0.01). These results suggest that acute intermittent stimulation of NTS neurons can induce renal sympathetic and phrenic LTF in the absence of hypoxia or chemoreceptor afferent activation. We also found that while acute intermittent optogenetic and hypoxic stimulations increased respiration-related RSNA modulation (P < 0.01), they did not increase synchronization between central respiratory drive and RSNA. We conclude that mechanisms that induce LTF originate within the caudal NTS and extend to other interconnecting neuronal elements of the central nervous cardiorespiratory network.
急性间歇性低氧（AIH）可诱导交感神经和膈神经长期易化（LTF），其定义为神经放电持续增加。我们研究了在麻醉、迷走神经切断和机械通气的大鼠孤束核（NTS）中，用携带CaMKIIa、hChR2（H134R）和mCherry的腺相关病毒（AAV）标记的神经元进行急性间歇性光遗传学（AIO）刺激以及AIH的作用。我们测量了肾交感神经活动（RSNA）、膈神经活动（PNA）、功率谱密度和相干性，并进行了互相关测量，以确定AIO刺激和AIH如何影响PNA和RSNA之间的同步性。在平衡氮气中用10%氧气通气产生AIH 60分钟后，RSNA和PNA振幅分别增加了80%和130%（P<0.01）。AIO刺激60分钟后，RSNA和PNA振幅分别增加了60%和100%（P<0.01）。这些结果表明，在没有缺氧或化学感受器传入激活的情况下，急性间歇性刺激NTS神经元可诱导肾交感神经和膈神经LTF。我们还发现，虽然急性间歇性光遗传学刺激和低氧刺激增加了与呼吸相关的RSNA调制（P<0.01），但它们并未增加中枢呼吸驱动与RSNA之间的同步性。我们得出结论，诱导LTF的机制起源于尾侧NTS，并延伸至中枢神经心肺网络的其他相互连接的神经元元件。
