Aylwin M L, Horowitz J M, Bonham A C
Department of Internal Medicine, University of California, Davis 95616, USA.
J Neurophysiol. 1997 May;77(5):2539-48. doi: 10.1152/jn.1997.77.5.2539.
The nucleus of the solitary tract (NTS) is a principal site for coordinating the reflex control of autonomic function. The nucleus receives and organizes primary visceral (sensory) afferent inputs from the great vessels, heart, lung, and gastrointestinal organs. Glutamate, the excitatory neurotransmitter released by the primary afferent fibers, activates non-N-methyl-D-aspartate (non-NMDA) receptors on second-order neurons in the NTS. Still in question is whether NMDA receptors on the second-order neurons are also activated. Accordingly, the purpose of this study was to directly determine whether NMDA receptors contribute to synaptic transmission of primary visceral afferent input to second-order neurons in the NTS. Whole cell patch-clamp recordings were obtained from intermediate and caudal NTS neurons in rat coronal medullary slices. Excitatory postsynaptic currents (EPSCs) were evoked by stimulation of the solitary tract (1-25 V, 0.1 ms, 0.2 or 0.5 Hz) at membrane potentials ranging from -90 to +60 mV. In 28 of 32 neurons in which current-voltage relationships were obtained for solitary-tract-evoked EPSCs, the currents had short onset latencies (3.42 +/- 1.03 ms, mean +/- SD), indicating that they were the result of monosynaptic activation of second-order neurons. Solitary-tract-evoked EPSCs had both a fast and a slow component. The amplitude of the slow component was nonlinearly related to voltage (being revealed only at membrane potentials positive to -45 mV), blocked by the NMDA receptor antagonist DL-2-amino-5-monophosphovaleric acid (APV, 50 microM; n = 12; P = 0.0001), and enhanced in nominally Mg2+-free perfusate at membrane potentials negative to -45 mV (n = 5; P = 0.016), demonstrating that the slow component was mediated by NMDA receptors. The amplitude of the fast component was linearly related to voltage and blocked by the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX, 3 microM; n = 9; P = 0.0014), demonstrating that the fast component was mediated by non-NMDA receptors. The slow component of the EPSCs was not blocked by NBQX (n = 6; P = 0.134), nor was the fast component blocked by APV (n = 12; P = 0.124). These results show that both NMDA and non-NMDA receptors coexist on the same second-order NTS neurons and mediate primary visceral afferent transmission in the NTS. The participation of NMDA receptors suggests that second-order neurons in the NTS may have previously unrecognized integrative capabilities in the reflex control of autonomic function.
孤束核（NTS）是协调自主功能反射控制的主要部位。该核接收并整理来自大血管、心脏、肺和胃肠道器官的初级内脏（感觉）传入输入。谷氨酸是初级传入纤维释放的兴奋性神经递质，可激活NTS中二级神经元上的非N - 甲基 - D - 天冬氨酸（非NMDA）受体。二级神经元上的NMDA受体是否也被激活仍存在疑问。因此，本研究的目的是直接确定NMDA受体是否参与初级内脏传入输入到NTS中二级神经元的突触传递。从大鼠冠状髓质切片中的中间和尾侧NTS神经元获得全细胞膜片钳记录。在膜电位范围为 - 90至 + 60 mV时，通过刺激孤束（1 - 25 V，0.1 ms，0.2或0.5 Hz）诱发兴奋性突触后电流（EPSC）。在32个获得孤束诱发EPSC电流 - 电压关系的神经元中的28个中，电流具有短的起始潜伏期（3.42 +/- 1.03 ms，平均值 +/- 标准差），表明它们是二级神经元单突触激活的结果。孤束诱发的EPSC有一个快速成分和一个慢速成分。慢速成分的幅度与电压呈非线性关系（仅在膜电位高于 - 45 mV时显示），被NMDA受体拮抗剂DL - 2 - 氨基 - 5 - 单磷酸戊酸（APV，50 microM；n = 12；P = 0.0001）阻断，并且在膜电位低于 - 45 mV的名义上无Mg2 + 的灌流液中增强（n = 5；P = 0.016），表明慢速成分由NMDA受体介导。快速成分的幅度与电压呈线性关系，并被非NMDA受体拮抗剂2,3 - 二羟基 - 6 - 硝基 - 7 - 氨磺酰基苯并（F）喹喔啉（NBQX，3 microM；n = 9；P = 0.0014）阻断，表明快速成分由非NMDA受体介导。EPSC的慢速成分未被NBQX阻断（n = 6；P = 0.134），快速成分也未被APV阻断（n = 12；P = 0.124）。这些结果表明，NMDA和非NMDA受体共存于同一NTS二级神经元上，并介导NTS中的初级内脏传入传递。NMDA受体的参与表明，NTS中的二级神经元在自主功能的反射控制中可能具有以前未被认识到的整合能力。
